{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:25:49Z","timestamp":1787984749936,"version":"build-2784847793"},"reference-count":178,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Heilongjiang Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["LH2023C061"],"award-info":[{"award-number":["LH2023C061"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science and Technology Major Program","award":["2024ZD0530500"],"award-info":[{"award-number":["2024ZD0530500"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32570792"],"award-info":[{"award-number":["32570792"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62502128"],"award-info":[{"award-number":["62502128"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M760709"],"award-info":[{"award-number":["2024M760709"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heilongjiang Postdoctoral Fund","award":["LBH-Z24210"],"award-info":[{"award-number":["LBH-Z24210"]}]},{"name":"the Key Research and Development Program of Heilongjiang Province","award":["2024ZX12C27"],"award-info":[{"award-number":["2024ZX12C27"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tumor metastasis is the leading cause of death in cancer patients, with epithelial\u2013mesenchymal transition (EMT) playing a key role. To systematically elucidate the cellular mechanisms and molecular networks through which EMT drives metastasis across cancers, this study integrated transcriptomic data from over 1.2 million single cells across 265 samples representing 12 primary epithelial cancers, constructing a comprehensive pan-cancer single-cell atlas covering diverse stages and metastatic states. By analyzing the metastatic features and interaction networks of malignant epithelial cells and cancer-associated fibroblasts (CAFs), we identified cancer-specific metastasis-related gene sets. Based on these genes, multiple machine learning algorithms were applied to build cancer-specific and cross-cancer metastasis prediction models, leading to the development of the metastasis prediction score (MPS) and global metastasis prediction score (GMPS). Both scores showed excellent predictive performance in independent test and external validation cohorts. MPS exhibited higher cancer specificity, whereas GMPS showed stronger cross-cancer generalization. Moreover, elevated MPS and GMPS reflected immunosuppressive tumor microenvironment features and were significantly associated with poor prognosis across multiple cancer types. Finally, through a drug repositioning framework, we identified several potential anti-metastatic compounds targeting the metastasis network, among which Fostamatinib demonstrated broad-spectrum therapeutic potential against metastasis in multiple cancers.<\/jats:p>","DOI":"10.3390\/ijms262311582","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:13:49Z","timestamp":1764576829000},"page":"11582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Construction of Metastasis Prediction Models and Screening of Anti-Metastatic Drugs Based on Pan-Cancer Single-Cell EMT Features"],"prefix":"10.3390","volume":"26","author":[{"given":"Yingqi","family":"Xu","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9031-1864","authenticated-orcid":false,"given":"Yawen","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maohao","family":"Li","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichao","family":"Wan","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8390-1403","authenticated-orcid":false,"given":"Xing","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congxue","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/494131a","article-title":"Tracking metastasis and tricking cancer","volume":"494","author":"Marx","year":"2013","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.cell.2011.09.024","article-title":"Tumor metastasis: Molecular insights and evolving paradigms","volume":"147","author":"Valastyan","year":"2011","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/nm1469","article-title":"Tumor metastasis: Mechanistic insights and clinical challenges","volume":"12","author":"Steeg","year":"2006","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.cell.2016.11.037","article-title":"Emerging biological principles of metastasis","volume":"168","author":"Lambert","year":"2017","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41591-020-01195-4","article-title":"Targeting metastatic cancer","volume":"27","author":"Ganesh","year":"2021","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nrc.2016.25","article-title":"Targeting metastasis","volume":"16","author":"Steeg","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cell.2016.06.028","article-title":"EMT: 2016","volume":"166","author":"Nieto","year":"2016","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/nm.4409","article-title":"Cancer stem cells revisited","volume":"23","author":"Batlle","year":"2017","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1007\/s00018-019-03398-6","article-title":"TGF\u03b2-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer","volume":"77","author":"Hua","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev-pathol-020117-043854","article-title":"Epithelial mesenchymal transition in tumor metastasis","volume":"13","author":"Mittal","year":"2018","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"35376","DOI":"10.18632\/oncotarget.15686","article-title":"Epithelial-mesenchymal transition in prostate cancer: An overview","volume":"8","author":"Montanari","year":"2017","journal-title":"Oncotarget"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.tcb.2015.07.012","article-title":"Epithelial\u2013mesenchymal plasticity: A central regulator of cancer progression","volume":"25","author":"Ye","year":"2015","journal-title":"Trends Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev-pathmechdis-051222-122423","article-title":"Update on epithelial-mesenchymal plasticity in cancer progression","volume":"19","author":"Fontana","year":"2024","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kang, E., Seo, J., Yoon, H., and Cho, S. (2021). The post-translational regulation of epithelial\u2013mesenchymal transition-inducing transcription factors in cancer metastasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073591"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Imani, S., Hosseinifard, H., Cheng, J., Wei, C., and Fu, J. (2016). Prognostic value of EMT-inducing transcription factors (EMT-TFs) in metastatic breast cancer: A systematic review and meta-analysis. Sci. Rep., 6.","DOI":"10.1038\/srep28587"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1186\/s12967-023-04575-9","article-title":"Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: Implications for novel therapeutic strategies","volume":"21","author":"Li","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41698-021-00200-4","article-title":"The pan-cancer landscape of crosstalk between epithelial-mesenchymal transition and immune evasion relevant to prognosis and immunotherapy response","volume":"5","author":"Wang","year":"2021","journal-title":"npj Precis. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shen, S., Liu, X., Guo, Q., Liang, Q., Wu, J., Guan, G., Zou, C., Zhu, C., Yan, Z., and Liu, T. (2023). Tumor microenvironment remodeling plus immunotherapy could be used in mesenchymal-like tumor with high tumor residual and drug resistant rate. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05667-4"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.cell.2011.11.025","article-title":"EMT and dissemination precede pancreatic tumor formation","volume":"148","author":"Rhim","year":"2012","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.cell.2017.10.044","article-title":"Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer","volume":"171","author":"Puram","year":"2017","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1186\/s13058-014-0407-9","article-title":"A signature of epithelial-mesenchymal plasticity and stromal activation in primary tumor modulates late recurrence in breast cancer independent of disease subtype","volume":"16","author":"Cheng","year":"2014","journal-title":"Breast Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Li, F., Song, Q.-Z., Zhang, Y.-F., Wang, X.-R., Cao, L.-M., Li, N., Zhao, L.-X., Zhang, S.-X., and Zhuang, X.-F. (2022). Identifying the EMT-related signature to stratify prognosis and evaluate the tumor microenvironment in lung adenocarcinoma. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1008416"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jung, A.R., Jung, C.-H., Noh, J.K., Lee, Y.C., and Eun, Y.-G. (2020). Epithelial-mesenchymal transition gene signature is associated with prognosis and tumor microenvironment in head and neck squamous cell carcinoma. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-60707-x"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial\u2013mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1038\/s41388-021-01728-2","article-title":"Isolating and targeting the real-time plasticity and malignant properties of epithelial-mesenchymal transition in cancer","volume":"40","author":"Esquer","year":"2021","journal-title":"Oncogene"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Huang, Z., Wu, C., Liu, X., Lu, S., You, L., Guo, F., Stalin, A., Zhang, J., Zhang, F., and Wu, Z. (2022). Single-cell and bulk RNA sequencing reveal malignant epithelial cell heterogeneity and prognosis signatures in gastric carcinoma. Cells, 11.","DOI":"10.3390\/cells11162550"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00432-024-06015-7","article-title":"Single-cell transcriptomes of dissecting the intra-tumoral heterogeneity of breast cancer microenvironment","volume":"151","author":"Chen","year":"2024","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Datta, A., Deng, S., Gopal, V., Yap, K.C.-H., Halim, C.E., Lye, M.L., Ong, M.S., Tan, T.Z., Sethi, G., and Hooi, S.C. (2021). Cytoskeletal dynamics in epithelial-mesenchymal transition: Insights into therapeutic targets for cancer metastasis. Cancers, 13.","DOI":"10.3390\/cancers13081882"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Usman, S., Waseem, N.H., Nguyen, T.K.N., Mohsin, S., Jamal, A., Teh, M.-T., and Waseem, A. (2021). Vimentin is at the heart of epithelial mesenchymal transition (EMT) mediated metastasis. Cancers, 13.","DOI":"10.3390\/cancers13194985"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e13423","DOI":"10.1111\/cpr.13423","article-title":"Heterogeneity and plasticity of epithelial\u2013mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms","volume":"56","author":"Li","year":"2023","journal-title":"Cell Prolif."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"216234","DOI":"10.1016\/j.canlet.2023.216234","article-title":"Cancer-associated fibroblasts: Key criminals of tumor pre-metastatic niche","volume":"566","author":"Dong","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"216279","DOI":"10.1016\/j.canlet.2023.216279","article-title":"Cancer-associated fibroblasts: A key target to snatch victory from defeat in therapy resistance associated with the pancreatic cancer stroma","volume":"567","author":"Luo","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Szabo, P.M., Vajdi, A., Kumar, N., Tolstorukov, M.Y., Chen, B.J., Edwards, R., Ligon, K.L., Chasalow, S.D., Chow, K.-H., and Shetty, A. (2023). Cancer-associated fibroblasts are the main contributors to epithelial-to-mesenchymal signatures in the tumor microenvironment. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-28480-9"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/cas.15609","article-title":"The heterogeneity of cancer-associated fibroblast subpopulations: Their origins, biomarkers, and roles in the tumor microenvironment","volume":"114","author":"Yamamoto","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/ng.3818","article-title":"Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors","volume":"49","author":"Li","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nushtaeva, A., Ermakov, M., Abdurakhmanova, M., Troitskaya, O., Belovezhets, T., Varlamov, M., Gayner, T., Richter, V., and Koval, O. (2023). \u201cPulsed hypoxia\u201d gradually reprograms breast cancer fibroblasts into pro-tumorigenic cells via mesenchymal\u2013epithelial transition. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032494"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jcmgh.2023.01.006","article-title":"Cancer-associated fibroblasts in hepatocellular carcinoma and cholangiocarcinoma","volume":"15","author":"Ying","year":"2023","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"216723","DOI":"10.1016\/j.canlet.2024.216723","article-title":"Single-cell transcriptomic analysis reveals the landscape of epithelial-mesenchymal transition molecular heterogeneity in esophageal squamous cell carcinoma","volume":"587","author":"Guo","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1158\/0008-5472.CAN-23-3264","article-title":"Single-cell and spatial transcriptome profiling identifies the transcription factor BHLHE40 as a driver of EMT in metastatic colorectal cancer","volume":"84","author":"Yang","year":"2024","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1172\/JCI0215518","article-title":"Evidence that fibroblasts derive from epithelium during tissue fibrosis","volume":"110","author":"Iwano","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"14049","DOI":"10.1038\/ncomms14049","article-title":"Massively parallel digital transcriptional profiling of single cells","volume":"8","author":"Zheng","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"708036","DOI":"10.1155\/2012\/708036","article-title":"Significance of CD44 and CD24 as cancer stem cell markers: An enduring ambiguity","volume":"2012","author":"Jaggupilli","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Sang, X., Wu, F., Wu, D., Lin, S., Li, J., Zhao, N., Chen, X., and Xu, A. (2020). Human Hepatic Cancer Stem Cells (HCSCs) Markers Correlated With Immune Infiltrates Reveal Prognostic Significance of Hepatocellular Carcinoma. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00112"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Saha, S.K., Kim, K., Yang, G.-M., Choi, H.Y., and Cho, S.-G. (2018). Cytokeratin 19 (KRT19) has a Role in the Reprogramming of Cancer Stem Cell-Like Cells to Less Aggressive and More Drug-Sensitive Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051423"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13048-019-0590-5","article-title":"Thy-1 predicts poor prognosis and is associated with self-renewal in ovarian cancer","volume":"12","author":"Connor","year":"2019","journal-title":"J. Ovarian Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12943-023-01793-z","article-title":"EMT\/MET plasticity in cancer and Go-or-Grow decisions in quiescence: The two sides of the same coin?","volume":"22","author":"Akhmetkaliyev","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.mrrev.2011.05.002","article-title":"Initial steps of metastasis: Cell invasion and endothelial transmigration","volume":"728","author":"Krupitza","year":"2011","journal-title":"Mutat. Res.\/Rev. Mutat. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12943-016-0502-x","article-title":"Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications","volume":"15","author":"Maziveyi","year":"2016","journal-title":"Mol. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1186\/s13046-018-0988-8","article-title":"Epigenetic reprogramming of epithelial mesenchymal transition in triple negative breast cancer cells with DNA methyltransferase and histone deacetylase inhibitors","volume":"37","author":"Su","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kang, H., Kim, H., Lee, S., Youn, H., and Youn, B. (2019). Role of metabolic reprogramming in epithelial\u2013mesenchymal transition (EMT). Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20082042"},{"key":"ref_51","first-page":"727","article-title":"Biological role of metabolic reprogramming of cancer cells during epithelial-mesenchymal transition","volume":"41","author":"Li","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41580-018-0080-4","article-title":"New insights into the mechanisms of epithelial\u2013mesenchymal transition and implications for cancer","volume":"20","author":"Dongre","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.tcb.2018.12.001","article-title":"EMT Transition States during Tumor Progression and Metastasis","volume":"29","author":"Pastushenko","year":"2019","journal-title":"Trends Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/1878-0261.12093","article-title":"New insights into the role of EMT in tumor immune escape","volume":"11","author":"Terry","year":"2017","journal-title":"Mol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.pharmthera.2018.09.007","article-title":"Hybrid epithelial\/mesenchymal phenotypes promote metastasis and therapy resistance across carcinomas","volume":"194","author":"Jolly","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1084\/jem.20162024","article-title":"Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer","volume":"214","author":"Biffi","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1158\/2159-8290.CD-18-0710","article-title":"IL1-Induced JAK\/STAT Signaling Is Antagonized by TGF\u03b2 to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma","volume":"9","author":"Biffi","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/nrc3603","article-title":"The roles of TGF\u03b2 in the tumour microenvironment","volume":"13","author":"Pickup","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.bbrc.2016.02.096","article-title":"miR-1271 inhibits migration, invasion and epithelial-mesenchymal transition by targeting ZEB1 and TWIST1 in pancreatic cancer cells","volume":"472","author":"Liu","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Xiao, L., Zhang, C., Li, X., Jia, C., Chen, L., Yuan, Y., Gao, Q., Lu, Z., Feng, Y., and Zhao, R. (2021). LEF1 Enhances the Progression of Colonic Adenocarcinoma via Remodeling the Cell Motility Associated Structures. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910870"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/j.ejca.2005.08.008","article-title":"The Fos family of transcription factors and their role in tumourigenesis","volume":"41","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Voronkova, M.A., Luanpitpong, S., Rojanasakul, L.W., Castranova, V., Dinu, C.Z., Riedel, H., and Rojanasakul, Y. (2017). SOX9 Regulates Cancer Stem-Like Properties and Metastatic Potential of Single-Walled Carbon Nanotube-Exposed Cells. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-12037-8"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1172\/JCI64410","article-title":"Transcription factor ATF3 links host adaptive response to breast cancer metastasis","volume":"123","author":"Wolford","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41423-021-00742-4","article-title":"Tissue-specific Tregs in cancer metastasis: Opportunities for precision immunotherapy","volume":"19","author":"Huppert","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41416-020-01048-4","article-title":"Cytotoxic CD8(+) T cells in cancer and cancer immunotherapy","volume":"124","author":"Raskov","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s12967-025-06167-1","article-title":"Role of CD4(+) T cells in cancer immunity: A single-cell sequencing exploration of tumor microenvironment","volume":"23","author":"An","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Xiao, Z., Wang, R., Wang, X., Yang, H., Dong, J., He, X., Yang, Y., Guo, J., Cui, J., and Zhou, Z. (2023). Impaired function of dendritic cells within the tumor microenvironment. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1213629"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/s41422-020-0343-4","article-title":"Immune checkpoint signaling and cancer immunotherapy","volume":"30","author":"He","year":"2020","journal-title":"Cell Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13073-025-01501-0","article-title":"Developing a novel aging assessment model to uncover heterogeneity in organ aging and screening of aging-related drugs","volume":"17","author":"Xu","year":"2025","journal-title":"Genome Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1158\/0008-5472.CAN-18-2636","article-title":"Spleen Tyrosine Kinase-Mediated Autophagy Is Required for Epithelial-Mesenchymal Plasticity and Metastasis in Breast Cancer","volume":"79","author":"Shinde","year":"2019","journal-title":"Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"122078","DOI":"10.1016\/j.lfs.2023.122078","article-title":"Integrated proteomics and phosphoproteomics analyses of esophageal cancer cells with different invasive abilities","volume":"332","author":"Xu","year":"2023","journal-title":"Life Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7907","DOI":"10.1158\/0008-5472.CAN-07-0331","article-title":"Syk tyrosine kinase is linked to cell motility and progression in squamous cell carcinomas of the head and neck","volume":"67","author":"Luangdilok","year":"2007","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Bacolod, M.D., and Barany, F. (2021). A Unified Transcriptional, Pharmacogenomic, and Gene Dependency Approach to Decipher the Biology, Diagnostic Markers, and Therapeutic Targets Associated with Prostate Cancer Metastasis. Cancers, 13.","DOI":"10.3390\/cancers13205158"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.7150\/ijms.105193","article-title":"In Silico Identification of ANKRD22 as a Theragnostic Target for Pancreatic Cancer and Fostamatinib\u2019s Therapeutic Potential","volume":"22","author":"Huynh","year":"2025","journal-title":"Int. J. Med. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-3-642-45195-9_14","article-title":"Chemoprevention of prostate cancer with the polyamine synthesis inhibitor difluoromethylornithine","volume":"202","author":"Meyskens","year":"2014","journal-title":"Recent Results Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1158\/1055-9965.EPI-07-0658","article-title":"The effect of difluoromethylornithine on decreasing prostate size and polyamines in men: Results of a year-long phase IIb randomized placebo-controlled chemoprevention trial","volume":"17","author":"Simoneau","year":"2008","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1089\/dna.2017.3790","article-title":"Trifluoperazine Activates FOXO1-Related Signals to Inhibit Tumor Growth in Hepatocellular Carcinoma","volume":"36","author":"Jiang","year":"2017","journal-title":"DNA Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/s12276-020-0447-4","article-title":"Targeting focal adhesion kinase in cancer cells and the tumor microenvironment","volume":"52","author":"Murphy","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.semcancer.2022.03.011","article-title":"The impact of VEGF on cancer metastasis and systemic disease","volume":"86","author":"Yang","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Termini, D., Den Hartogh, D.J., Jaglanian, A., and Tsiani, E. (2020). Curcumin against Prostate Cancer: Current Evidence. Biomolecules, 10.","DOI":"10.3390\/biom10111536"},{"key":"ref_81","first-page":"5482","article-title":"Troglitazone inhibits the migration and invasion of PC-3 human prostate cancer cells by upregulating E-cadherin and glutathione peroxidase 3","volume":"16","author":"Chang","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ccell.2017.07.005","article-title":"Genomic Evolution of Breast Cancer Metastasis and Relapse","volume":"32","author":"Yates","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.cell.2023.03.016","article-title":"Fibroblasts in cancer: Unity in heterogeneity","volume":"186","author":"Chhabra","year":"2023","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"114484","DOI":"10.1016\/j.intimp.2025.114484","article-title":"EGR2 promotes liver cancer metastasis by enhancing IL-8 expression through transcription regulation of PDK4 in M2 macrophages","volume":"153","author":"Wei","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Wang, S., Wan, L., Zhang, X., Fang, H., Zhang, M., Li, F., and Yan, D. (2025). ETS-1 in tumor immunology: Implications for novel anti-cancer strategies. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1526368"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s00280-013-2091-3","article-title":"A multi-histology trial of fostamatinib in patients with advanced colorectal, non-small cell lung, head and neck, thyroid, and renal cell carcinomas, and pheochromocytomas","volume":"71","author":"Park","year":"2013","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Regan-Fendt, K., Li, D., Reyes, R., Yu, L., Wani, N.A., Hu, P., Jacob, S.T., Ghoshal, K., Payne, P.R.O., and Motiwala, T. (2020). Transcriptomics-Based Drug Repurposing Approach Identifies Novel Drugs against Sorafenib-Resistant Hepatocellular Carcinoma. Cancers, 12.","DOI":"10.3390\/cancers12102730"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4895","DOI":"10.21873\/anticanres.17315","article-title":"Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction","volume":"44","author":"Lee","year":"2024","journal-title":"Anticancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"D870","DOI":"10.1093\/nar\/gkac947","article-title":"CellMarker 2.0: An updated database of manually curated cell markers in human\/mouse and web tools based on scRNA-seq data","volume":"51","author":"Hu","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.1254257","article-title":"Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma","volume":"344","author":"Patel","year":"2014","journal-title":"Science"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.cell.2020.03.048","article-title":"Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer","volume":"181","author":"Zhang","year":"2020","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s12943-024-02062-3","article-title":"Single-cell tumor heterogeneity landscape of hepatocellular carcinoma: Unraveling the pro-metastatic subtype and its interaction loop with fibroblasts","volume":"23","author":"Guo","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"H\u00e4nzelmann, S., Castelo, R., and Guinney, J. (2013). GSVA: Gene set variation analysis for microarray and RNA-seq data. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-7"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1126\/science.aax0249","article-title":"Single-cell transcriptional diversity is a hallmark of developmental potential","volume":"367","author":"Gulati","year":"2020","journal-title":"Science"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.cell.2021.01.010","article-title":"A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells","volume":"184","author":"Cheng","year":"2021","journal-title":"Cell"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Gaujoux, R., and Seoighe, C. (2010). A flexible R package for nonnegative matrix factorization. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-367"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"100498","DOI":"10.1016\/j.crmeth.2023.100498","article-title":"hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data","volume":"3","author":"Morabito","year":"2023","journal-title":"Cell Rep. Methods"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: Single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Street, K., Risso, D., Fletcher, R.B., Das, D., Ngai, J., Yosef, N., Purdom, E., and Dudoit, S. (2018). Slingshot: Cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4772-0"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Wolf, F.A., Angerer, P., and Theis, F.J. (2018). SCANPY: Large-scale single-cell gene expression data analysis. Genome Biol, 19.","DOI":"10.1186\/s13059-017-1382-0"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Pham, D., Tan, X., Xu, J., Grice, L.F., Lam, P.Y., Raghubar, A., Vukovic, J., Ruitenberg, M.J., and Nguyen, Q. (2020). stLearn: Integrating spatial location, tissue morphology and gene expression to find cell types, cell-cell interactions and spatial trajectories within undissociated tissues. bioRxiv.","DOI":"10.1101\/2020.05.31.125658"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1038\/s41587-022-01273-7","article-title":"Spatially informed cell-type deconvolution for spatial transcriptomics","volume":"40","author":"Ma","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Kerseviciute, I., and Gordevicius, J. (2023). aPEAR: An R package for autonomous visualization of pathway enrichment networks. Bioinformatics, 39.","DOI":"10.1093\/bioinformatics\/btad672"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","article-title":"The sva package for removing batch effects and other unwanted variation in high-throughput experiments","volume":"28","author":"Leek","year":"2012","journal-title":"Bioinform."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization Paths for Generalized Linear Models via Coordinate Descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J. Stat. Softw."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1021\/ci034160g","article-title":"Random Forest:\u2009 A Classification and Regression Tool for Compound Classification and QSAR Modeling","volume":"43","author":"Svetnik","year":"2003","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i11","article-title":"Feature Selection with Boruta Package","volume":"36","author":"Kursa","year":"2010","journal-title":"J. Stat. Softw."},{"key":"ref_113","unstructured":"Dimitriadou, E., Hornik, K., Leisch, F., Meyer, D., and Weingessel, A. (2009). E1071: Misc Functions of the Department of Statistics (E1071), TU Wien."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building Predictive Models in R Using the caret Package","volume":"28","author":"Kuhn","year":"2008","journal-title":"J. Stat. Softw."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Chen, T., and Guestrin, C. (2016, January 13\u201317). XGBoost: A Scalable Tree Boosting System. Proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, San Francisco, CA, USA.","DOI":"10.1145\/2939672.2939785"},{"key":"ref_116","unstructured":"Ke, G., Meng, Q., Finley, T., Wang, T., Chen, W., Ma, W., Ye, Q., and Liu, T.-Y. (2017, January 4\u20139). LightGBM: A highly efficient gradient boosting decision tree. Proceedings of the 31st International Conference on Neural Information Processing Systems, Long Beach, CA, USA."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/323533a0","article-title":"Learning representations by back-propagating errors","volume":"323","author":"Rumelhart","year":"1986","journal-title":"Nature"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Zeng, D., Ye, Z., Shen, R., Yu, G., Wu, J., Xiong, Y., Zhou, R., Qiu, W., Huang, N., and Sun, L. (2021). IOBR: Multi-Omics Immuno-Oncology Biological Research to Decode Tumor Microenvironment and Signatures. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.687975"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.ajhg.2008.02.013","article-title":"Walking the interactome for prioritization of candidate disease genes","volume":"82","author":"Bauer","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.cell.2017.10.049","article-title":"A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles","volume":"171","author":"Subramanian","year":"2017","journal-title":"Cell"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41389-021-00355-6","article-title":"Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis","volume":"10","author":"Xu","year":"2021","journal-title":"Oncogenesis"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e2205395","DOI":"10.1002\/advs.202205395","article-title":"Combined Single-Cell and Spatial Transcriptomics Reveal the Metabolic Evolvement of Breast Cancer during Early Dissemination","volume":"10","author":"Liu","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/s41588-021-00911-1","article-title":"A single-cell and spatially resolved atlas of human breast cancers","volume":"53","author":"Wu","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/s41698-024-00723-6","article-title":"Serial single-cell RNA sequencing unveils drug resistance and metastatic traits in stage IV breast cancer","volume":"8","author":"Otsuji","year":"2024","journal-title":"NPJ Precis. Oncol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ccell.2024.02.002","article-title":"PDGFR\u03b1(+)ITGA11(+) fibroblasts foster early-stage cancer lymphovascular invasion and lymphatic metastasis via ITGA11-SELE interplay","volume":"42","author":"Zheng","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1002\/ijc.33794","article-title":"Single-cell RNA sequencing reveals the epithelial cell heterogeneity and invasive subpopulation in human bladder cancer","volume":"149","author":"Lai","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1158\/0008-5472.CAN-22-3034","article-title":"Mesenchymal-like Tumor Cells and Myofibroblastic Cancer-Associated Fibroblasts Are Associated with Progression and Immunotherapy Response of Clear Cell Renal Cell Carcinoma","volume":"83","author":"Davidson","year":"2023","journal-title":"Cancer Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.eururo.2023.02.008","article-title":"Single-cell Deconvolution of a Specific Malignant Cell Population as a Poor Prognostic Biomarker in Low-risk Clear Cell Renal Cell Carcinoma Patients","volume":"83","author":"Saout","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.ccell.2021.02.015","article-title":"Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma","volume":"39","author":"Bi","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.ccell.2021.03.007","article-title":"Single-cell sequencing links multiregional immune landscapes and tissue-resident T cells in ccRCC to tumor topology and therapy efficacy","volume":"39","author":"Krishna","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1158\/0008-5472.CAN-23-2123","article-title":"Th17 Cells Secrete TWEAK to Trigger Epithelial-Mesenchymal Transition and Promote Colorectal Cancer Liver Metastasis","volume":"84","author":"Liu","year":"2024","journal-title":"Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Khaliq, A.M., Erdogan, C., Kurt, Z., Turgut, S.S., Grunvald, M.W., Rand, T., Khare, S., Borgia, J.A., Hayden, D.M., and Pappas, S.G. (2022). Refining colorectal cancer classification and clinical stratification through a single-cell atlas. Genome Biol., 23, Correction in Genome Biol. 2022, 23, 156.","DOI":"10.1186\/s13059-022-02724-9"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13073-024-01320-9","article-title":"Single-cell profiling of response to neoadjuvant chemo-immunotherapy in surgically resectable esophageal squamous cell carcinoma","volume":"16","author":"Ji","year":"2024","journal-title":"Genome Med."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Kang, B., Camps, J., Fan, B., Jiang, H., Ibrahim, M.M., Hu, X., Qin, S., Kirchhoff, D., Chiang, D.Y., and Wang, S. (2022). Parallel single-cell and bulk transcriptome analyses reveal key features of the gastric tumor microenvironment. Genome Biol., 23.","DOI":"10.1186\/s13059-022-02828-2"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1158\/2159-8290.CD-21-0683","article-title":"Single-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric Cancer","volume":"12","author":"Kumar","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1038\/s41388-024-03114-0","article-title":"Single-cell profiling reveals altered immune landscape and impaired NK cell function in gastric cancer liver metastasis","volume":"43","author":"Tang","year":"2024","journal-title":"Oncogene"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4594","DOI":"10.1038\/s41467-022-32283-3","article-title":"A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma","volume":"13","author":"Lu","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41421-023-00529-z","article-title":"CD36(+) cancer-associated fibroblasts provide immunosuppressive microenvironment for hepatocellular carcinoma via secretion of macrophage migration inhibitory factor","volume":"9","author":"Zhu","year":"2023","journal-title":"Cell Discov."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1038\/s41467-023-37379-y","article-title":"Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis","volume":"14","author":"Quah","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e2204514","DOI":"10.1002\/advs.202204514","article-title":"Ferroptosis Signature Shapes the Immune Profiles to Enhance the Response to Immune Checkpoint Inhibitors in Head and Neck Cancer","volume":"10","author":"Chung","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/s41467-023-36691-x","article-title":"Single-cell transcriptome profiling of the stepwise progression of head and neck cancer","volume":"14","author":"Choi","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Sun, Y., Chen, S., Lu, Y., Xu, Z., Fu, W., and Yan, W. (2024). Single-cell transcriptomic analyses of tumor microenvironment and molecular reprograming landscape of metastatic laryngeal squamous cell carcinoma. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-05765-x"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"105348","DOI":"10.1016\/j.oraloncology.2021.105348","article-title":"Single-cell profiling of tumor-infiltrating TCF1\/TCF7(+) T cells reveals a T lymphocyte subset associated with tertiary lymphoid structures\/organs and a superior prognosis in oral cancer","volume":"119","author":"Peng","year":"2021","journal-title":"Oral Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e003534","DOI":"10.1136\/jitc-2021-003534","article-title":"Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma","volume":"10","author":"Yang","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12943-025-02287-w","article-title":"Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer","volume":"24","author":"Cui","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"3590","DOI":"10.1158\/1078-0432.CCR-22-0296","article-title":"Single-Cell RNA Sequencing Reveals the Tissue Architecture in Human High-Grade Serous Ovarian Cancer","volume":"28","author":"Xu","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"4924","DOI":"10.1016\/j.molcel.2021.10.013","article-title":"A multi-omic single-cell landscape of human gynecologic malignancies","volume":"81","author":"Regner","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/s41422-020-0355-0","article-title":"A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling","volume":"30","author":"Qian","year":"2020","journal-title":"Cell Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12943-024-02003-0","article-title":"Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications","volume":"23","author":"Park","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13073-020-00776-9","article-title":"Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions","volume":"12","author":"Lin","year":"2020","journal-title":"Genome Med."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"5123","DOI":"10.1038\/s41467-023-40727-7","article-title":"Single cell transcriptomic analyses implicate an immunosuppressive tumor microenvironment in pancreatic cancer liver metastasis","volume":"14","author":"Zhang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41467-023-36325-2","article-title":"Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses","volume":"14","author":"Hirz","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41556-020-00613-6","article-title":"Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression","volume":"23","author":"Chen","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1158\/0008-5472.CAN-22-2682","article-title":"Spatial Transcriptomic Analysis of a Diverse Patient Cohort Reveals a Conserved Architecture in Triple-Negative Breast Cancer","volume":"83","author":"Bassiouni","year":"2023","journal-title":"Cancer Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.immuni.2022.02.001","article-title":"Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer","volume":"55","author":"Meylan","year":"2022","journal-title":"Immunity"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1038\/s41588-022-01141-9","article-title":"Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment","volume":"54","author":"Barkley","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Shi, Q., Liu, Y., Lu, M., Lei, Q.Y., Chen, Z., Wang, L., and He, X. (2022). A pathway-guided strategy identifies a metabolic signature for prognosis prediction and precision therapy for hepatocellular carcinoma. Comput. Biol. Med., 144.","DOI":"10.1016\/j.compbiomed.2022.105376"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"13550","DOI":"10.1073\/pnas.0506230102","article-title":"An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival","volume":"102","author":"Miller","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Li, H., Liu, S., Li, C., Xiao, Z., Hu, J., and Zhao, C. (2021). TNF Family-Based Signature Predicts Prognosis, Tumor Microenvironment, and Molecular Subtypes in Bladder Carcinoma. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.800967"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"5262","DOI":"10.1038\/s41467-021-25618-z","article-title":"Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma","volume":"12","author":"Sun","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1053\/j.gastro.2009.11.005","article-title":"Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer","volume":"138","author":"Smith","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1038\/s41467-020-17227-z","article-title":"Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma","volume":"11","author":"Cao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Ooi, C.H., Ivanova, T., Wu, J., Lee, M., Tan, I.B., Tao, J., Ward, L., Koo, J.H., Gopalakrishnan, V., and Zhu, Y. (2009). Oncogenic pathway combinations predict clinical prognosis in gastric cancer. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000676"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/1878-0261.12153","article-title":"Tumor-adjacent tissue co-expression profile analysis reveals pro-oncogenic ribosomal gene signature for prognosis of resectable hepatocellular carcinoma","volume":"12","author":"Grinchuk","year":"2018","journal-title":"Mol. Oncol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1002\/ijc.29649","article-title":"The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer","volume":"137","author":"Wichmann","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"186ra166","DOI":"10.1126\/scitranslmed.3005723","article-title":"Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers","volume":"5","author":"Rousseaux","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Bowen, N.J., Walker, L.D., Matyunina, L.V., Logani, S., Totten, K.A., Benigno, B.B., and McDonald, J.F. (2009). Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells. BMC Med. Genom., 2.","DOI":"10.1186\/1755-8794-2-71"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.molonc.2016.05.004","article-title":"RNA sequencing of pancreatic adenocarcinoma tumors yields novel expression patterns associated with long-term survival and reveals a role for ANGPTL4","volume":"10","author":"Kirby","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Erho, N., Crisan, A., Vergara, I.A., Mitra, A.P., Ghadessi, M., Buerki, C., Bergstralh, E.J., Kollmeyer, T., Fink, S., and Haddad, Z. (2013). Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066855"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/j.cell.2020.10.036","article-title":"Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy","volume":"183","author":"Krug","year":"2020","journal-title":"Cell"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Clark, D.J., Dhanasekaran, S.M., Petralia, F., Pan, J., Song, X., Hu, Y., da Veiga Leprevost, F., Reva, B., Lih, T.-S.M., and Chang, H.Y. (2019). Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma. Cell, 179, Erratum in Cell 2020, 180, 207.","DOI":"10.1016\/j.cell.2019.10.007"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.cell.2019.03.030","article-title":"Proteogenomic Analysis of Human Colon Cancer Reveals New Therapeutic Opportunities","volume":"177","author":"Vasaikar","year":"2019","journal-title":"Cell"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.ccell.2020.12.007","article-title":"Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma","volume":"39","author":"Huang","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"4348","DOI":"10.1016\/j.cell.2021.07.016","article-title":"A proteogenomic portrait of lung squamous cell carcinoma","volume":"184","author":"Satpathy","year":"2021","journal-title":"Cell"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.cell.2016.05.069","article-title":"Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer","volume":"166","author":"Zhang","year":"2016","journal-title":"Cell"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"5031","DOI":"10.1016\/j.cell.2021.08.023","article-title":"Proteogenomic characterization of pancreatic ductal adenocarcinoma","volume":"184","author":"Cao","year":"2021","journal-title":"Cell"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12014-024-09450-3","article-title":"Frozen tissue coring and layered histological analysis improves cell type-specific proteogenomic characterization of pancreatic adenocarcinoma","volume":"21","author":"Savage","year":"2024","journal-title":"Clin Proteom."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11582\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T05:24:03Z","timestamp":1764739443000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,29]]},"references-count":178,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311582"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311582","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,29]]}}}