{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:07:57Z","timestamp":1791972477680,"version":"4.3.4"},"reference-count":63,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background: Gastric cancer (GC) represents a significant global health burden with considerable heterogeneity in clinical and molecular behavior. The anatomical site of tumor origin\u2014proximal versus distal\u2014has emerged as a determinant of prognosis and response to therapy. The aim of this paper is to elucidate the transcriptional and regulatory differences between proximal gastric cancer (PGC) and distal gastric cancer (DGC) through master regulator (MR) analysis. Methods: We analyzed RNA-seq data from TCGA-STAD and microarray data from GEO (GSE62254, GSE15459). Differential gene expression and MR analyses were performed using DESeq2, limma, corto, and RegEnrich pipelines. A harmonized matrix of 4785 genes was used for MR inference following normalization and batch correction. Functional enrichment and survival analyses were conducted to explore prognostic associations. Results: Among 364 TCGA and 492 GEO patients, PGC was associated with more aggressive clinicopathological features and poorer outcomes. We identified 998 DEGs distinguishing PGC and DGC. PGC showed increased FOXM1 (a key regulator of cell proliferation), STAT3, and NF-\u03baB1 activity, while DGC displayed enriched GATA6, CDX2 (a marker of intestinal differentiation), and HNF4A signaling. Functional enrichment highlighted proliferative and inflammatory programs in PGC, and differentiation and metabolic pathways in DGC. MR activity stratified survival outcomes, reinforcing prognostic relevance. Conclusions: PGC and DGC are governed by distinct transcriptional regulators and signaling networks. Our findings provide a biological rationale for location-based stratification and inform targeted therapy development.<\/jats:p>","DOI":"10.3390\/curroncol32080424","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T14:05:47Z","timestamp":1753711547000},"page":"424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Different Master Regulators Define Proximal and Distal Gastric Cancer: Insights into Prognosis and Opportunities for Targeted Therapy"],"prefix":"10.3390","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9777-9588","authenticated-orcid":false,"given":"Luigi","family":"Marano","sequence":"first","affiliation":[{"name":"Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS (Akademia Medycznych I Spolecznych Nauk Stosowanych), 52-300 Elbl\u0105g, Poland"},{"name":"Department of General Surgery and Surgical Oncology, \u201cSaint Wojciech\u201d Hospital, \u201cNicolaus Copernicus\u201d Health Center, 80-000 Gda\u0144sk, Poland"},{"name":"Department of Surgery, Dnipro State Medical University, 49044 Dnipro, Ukraine"},{"name":"Department of Medicine, Surgery, and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0427-6648","authenticated-orcid":false,"given":"Salvatore","family":"Sorrenti","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cSapienza\u201d University of Rome, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6462-2090","authenticated-orcid":false,"given":"Silvia","family":"Malerba","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari \u201cAldo Moro\u201d, 70110 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw","family":"Skokowski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS (Akademia Medycznych I Spolecznych Nauk Stosowanych), 52-300 Elbl\u0105g, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol","family":"Polom","sequence":"additional","affiliation":[{"name":"Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS (Akademia Medycznych I Spolecznych Nauk Stosowanych), 52-300 Elbl\u0105g, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0988-5875","authenticated-orcid":false,"given":"Sergii","family":"Girnyi","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical Oncology, \u201cSaint Wojciech\u201d Hospital, \u201cNicolaus Copernicus\u201d Health Center, 80-000 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-9735","authenticated-orcid":false,"given":"Tomasz","family":"Cwalinski","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical Oncology, \u201cSaint Wojciech\u201d Hospital, \u201cNicolaus Copernicus\u201d Health Center, 80-000 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Paolo","family":"Prete","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari \u201cAldo Moro\u201d, 70110 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Gonz\u00e1lez-Ojeda","sequence":"additional","affiliation":[{"name":"Department of Surgery, Centro M\u00e9dico Nacional de Occidente IMSS, Guadalajara 44329, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clotilde","family":"Fuentes-Orozco","sequence":"additional","affiliation":[{"name":"Department of Surgery, Centro M\u00e9dico Nacional de Occidente IMSS, Guadalajara 44329, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7336-1366","authenticated-orcid":false,"given":"Aman","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Mahatma Gandhi Medical College and Research Institute, Puducherry 607402, India"},{"name":"Department of Medicine, Adesh Institute of Medical Sciences and Research, Bathinda 151001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajan","family":"Vaithianathan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Mahatma Gandhi Medical College and Research Institute, Puducherry 607402, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miljana","family":"Vladimirov","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Bielefeld\u2014Campus Lippe, 32756 Detmold, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1943-4952","authenticated-orcid":false,"given":"Eleonora","family":"Lori","sequence":"additional","affiliation":[{"name":"Department of Surgery, Sapienza University of Rome, AOU Policlinico Umberto I, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1545-0779","authenticated-orcid":false,"given":"Daniele","family":"Pironi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Sapienza University of Rome, AOU Policlinico Umberto I, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3408-4540","authenticated-orcid":false,"given":"Adel","family":"Abou-Mrad","sequence":"additional","affiliation":[{"name":"Department of Surgery, Centre Hospitalier Universitaire d\u2019Orl\u00e9ans, 45000 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9297-4894","authenticated-orcid":false,"given":"Mario","family":"Testini","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari \u201cAldo Moro\u201d, 70110 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3784-6555","authenticated-orcid":false,"given":"Rodolfo J.","family":"Oviedo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nacogdoches Medical Center, Nacogdoches, TX 75962, USA"},{"name":"Department of Surgery, Tilman J. Fertitta Family College of Medicine, University of Houston, Houston, TX 77001, USA"},{"name":"Department of Surgery, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2030-6712","authenticated-orcid":false,"given":"Yogesh","family":"Vashist","sequence":"additional","affiliation":[{"name":"Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS (Akademia Medycznych I Spolecznych Nauk Stosowanych), 52-300 Elbl\u0105g, Poland"},{"name":"Department of Surgical Oncology, Asklepios Harz Clinic Goslar, 38640 Goslar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Qin, N., Fan, Y., Yang, T., Yang, Z., and Fan, D. (2025). The Burden of Gastric Cancer and Possible Risk Factors from 1990 to 2021, and Projections until 2035: Findings from the Global Burden of Disease Study 2021. Biomark. Res., 13.","DOI":"10.1186\/s40364-024-00720-8"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hsu, J.-T., Lin, Y.-N., Chen, Y.-F., Kou, H.-W., Wang, S.-Y., Chou, W.-C., Wu, T.-R., and Yeh, T.-S. (2024). A Comprehensive Overview of Gastric Cancer Management from a Surgical Point of View. Biomed. J.","DOI":"10.1016\/j.bj.2024.100817"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/apm.1965.64.1.31","article-title":"The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification","volume":"64","author":"Lauren","year":"1965","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/his.13975","article-title":"The 2019 WHO Classification of Tumours of the Digestive System","volume":"76","author":"Nagtegaal","year":"2019","journal-title":"Histopathology"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhang, N., Wang, D., Hu, X., Zhang, G., Li, Z., Zhao, Y., Liu, Z., and Wang, Y. (2022). Analysis of Immune Status in Gastric Adenocarcinoma with Different Infiltrating Patterns and Origin Sites. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.978715"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12957-021-02126-4","article-title":"Comparison of the Overall Survival of Proximal and Distal Gastric Cancer after Gastrectomy: A Systematic Review and Meta-Analysis","volume":"19","author":"Xue","year":"2021","journal-title":"World J. Surg. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.7150\/jca.30371","article-title":"Comparison on Clinicopathological Features, Treatments and Prognosis between Proximal Gastric Cancer and Distal Gastric Cancer: A National Cancer Data Base Analysis","volume":"10","author":"Wang","year":"2019","journal-title":"J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5","DOI":"10.5230\/jgc.2025.25.e11","article-title":"Korean Practice Guidelines for Gastric Cancer 2024: An Evidence-Based, Multidisciplinary Approach (Update of 2022 Guideline)","volume":"25","author":"Kim","year":"2025","journal-title":"J. Gastric Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yoo, S., Chen, Q., Wang, L., Wang, W., Chakravarthy, A., Busuttil, R., Boussioutas, A., Liu, D., She, J., and Fenton, T.R. (2020). Molecular and Cellular Heterogeneity of Gastric Cancer Explained by Methylation-Driven Key Regulators. bioRxiv.","DOI":"10.1101\/2020.01.27.920744"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Begolli, R., Patouna, A., Vardakas, P., Xagara, A., Apostolou, K., Kouretas, D., and Giakountis, A. (2024). Deciphering the Landscape of GATA-Mediated Transcriptional Regulation in Gastric Cancer. Antioxidants, 13.","DOI":"10.3390\/antiox13101267"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s10020-022-00468-7","article-title":"The Dynamic Alteration of Transcriptional Regulation by Crucial TFs during Tumorigenesis of Gastric Cancer","volume":"28","author":"Yu","year":"2022","journal-title":"Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s10120-024-01523-4","article-title":"Potent Therapeutic Strategy in Gastric Cancer with Microsatellite Instability-High and\/or Deficient Mismatch Repair","volume":"27","author":"Ooki","year":"2024","journal-title":"Gastric Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Accordino, G., Lettieri, S., Bortolotto, C., Benvenuti, S., Gallotti, A., Gattoni, E., Agustoni, F., Pozzi, E., Rinaldi, P., and Primiceri, C. (2020). Cancers Review From Interconnection between Genes and Microenvironment to Novel Immunotherapeutic Approaches in Upper Gastro-Intestinal Cancers-A Multidisciplinary Perspective. Cancers, 12.","DOI":"10.3390\/cancers12082105"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"D\u00edaz del Arco, C., Fern\u00e1ndez Ace\u00f1ero, M.J., and Ortega Medina, L. (2024). Molecular Classifications in Gastric Cancer: A Call for Interdisciplinary Collaboration. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052649"},{"key":"ref_15","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":"Bioinformatics"},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"3916","DOI":"10.1093\/bioinformatics\/btaa223","article-title":"Corto: A Lightweight R Package for Gene Network Inference and Master Regulator Analysis","volume":"36","author":"Mercatelli","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_18","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 A J. Integr. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1093\/bioinformatics\/btr260","article-title":"Molecular Signatures Database (MSigDB) 3.0","volume":"27","author":"Liberzon","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New Perspectives on Genomes, Pathways, Diseases and Drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: Tool for the Unification of Biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e00295","DOI":"10.14309\/ctg.0000000000000295","article-title":"Meta-Analysis Reveals the Prognostic Relevance of Nuclear and Membrane-Associated Bile Acid Receptors in Gastric Cancer","volume":"12","author":"Rohr","year":"2021","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jafari, N., Abediankenari, S., Hosseini-Khah, Z., Valizadeh, S.M., Torabizadeh, Z., Zaboli, E., Ghasemi, M., Fakheri, H., Hosseini, V., and Shekarriz, R. (2020). Expression Patterns of Seven Key Genes, Including \u03b2-Catenin, Notch1, GATA6, CDX2, MiR-34a, MiR-181a and MiR-93 in Gastric Cancer. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-69308-0"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, J., Sun, S., Luo, Z., Zhang, P., Xu, Y., Qiu, Z., and Huang, C. (2023). Single-Cell Transcriptome Profiling Identifies Tumor Heterogeneity in Epithelial, Stromal and Immune Cells Between Distal and Proximal Gastric Cancer. iScience.","DOI":"10.2139\/ssrn.4360364"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3748\/wjg.v10.i1.17","article-title":"Differences in Proximal (Cardia) versus Distal (Antral) Gastric Carcinogenesis via Retinoblastoma Pathway","volume":"10","author":"Gulmann","year":"2004","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1245\/s10434-017-5832-4","article-title":"Prognostic Role of Primary Tumor Location in Non-Metastatic Gastric Cancer: A Systematic Review and Meta-Analysis of 50 Studies","volume":"24","author":"Petrelli","year":"2017","journal-title":"Ann. Surg. Oncol."},{"key":"ref_28","first-page":"146","article-title":"Prognostic Factors for Survival in Patients with Gastric Cancer: Single-Centre Experience","volume":"7","author":"Yaprak","year":"2019","journal-title":"N. Clin. Istanb."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.21873\/invivo.13035","article-title":"Clinicopathological Prognostic Factors Determining Outcomes of Treatment in Gastric Cancer Surgery","volume":"36","author":"Kulig","year":"2022","journal-title":"In Vivo"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1158\/0008-5472.CAN-08-3045","article-title":"Critical Role and Regulation of Transcription Factor Foxm1 in Human Gastric Cancer Angiogenesis and Progression","volume":"69","author":"Li","year":"2009","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/1479-5876-11-204","article-title":"Forkhead Box Transcription Factor 1 Expression in Gastric Cancer: FOXM1 Is a Poor Prognostic Factor and Mediates Resistance to Docetaxel","volume":"11","author":"Li","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"32298","DOI":"10.18632\/oncotarget.15764","article-title":"Prognostic Value of FOXM1 in Solid Tumors: A Systematic Review and Meta-Analysis","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16975","DOI":"10.1073\/pnas.1315862110","article-title":"STAT3 Activation in Response to IL-6 Is Prolonged by the Binding of IL-6 Receptor to EGF Receptor","volume":"110","author":"Wang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1089\/jir.2014.0225","article-title":"STAT3-Activating Cytokines: A Therapeutic Opportunity for Inflammatory Bowel Disease?","volume":"35","author":"Nguyen","year":"2015","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1016\/j.ejca.2005.08.016","article-title":"The Role of IL-6 and STAT3 in Inflammation and Cancer","volume":"41","author":"Hodge","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1248\/bpb.b22-00887","article-title":"The Physiological and Pathophysiological Role of IL-6\/STAT3-Mediated Signal Transduction and STAT3 Binding Partners in Therapeutic Applications","volume":"46","author":"Matsuda","year":"2023","journal-title":"Biol. Pharm. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12943-016-0561-z","article-title":"STAT3 Signaling Drives EZH2 Transcriptional Activation and Mediates Poor Prognosis in Gastric Cancer","volume":"15","author":"Pan","year":"2016","journal-title":"Mol. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/mco2.104","article-title":"NF-\u03baB Signaling in Inflammation and Cancer","volume":"2","author":"Zhang","year":"2021","journal-title":"MedComm"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ni, Y., Low, J.T., Silke, J., and O\u2019Reilly, L.A. (2022). Digesting the Role of JAK-STAT and Cytokine Signaling in Oral and Gastric Cancers. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.835997"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e37263","DOI":"10.1016\/j.heliyon.2024.e37263","article-title":"Induction, Growth, Drug Resistance, and Metastasis: A Comprehensive Summary of the Relationship between STAT3 and Gastric Cancer","volume":"10","author":"Chen","year":"2024","journal-title":"Heliyon"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rah, B., Rather, R.A., Bhat, G.R., Baba, A.B., Mushtaq, I., Farooq, M., Yousuf, T., Dar, S.B., Parveen, S., and Hassan, R. (2022). JAK\/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.821344"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"111717","DOI":"10.1016\/j.intimp.2024.111717","article-title":"Preclinical Development and Clinical Studies of Targeted JAK\/STAT Combined Anti-PD-1\/PD-L1 Therapy","volume":"130","author":"Chen","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"122635","DOI":"10.1016\/j.lfs.2024.122635","article-title":"Enhancing Cancer Therapy: The Role of Drug Delivery Systems in STAT3 Inhibitor Efficacy and Safety","volume":"346","author":"Wang","year":"2024","journal-title":"Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13008-024-00125-x","article-title":"Mitotic Kinases Are Emerging Therapeutic Targets against Metastatic Breast Cancer","volume":"19","author":"Saavedra","year":"2024","journal-title":"Cell Div."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/mco2.55","article-title":"Molecular Mechanisms of Chemo- and Radiotherapy Resistance and the Potential Implications for Cancer Treatment","volume":"2","author":"Liu","year":"2021","journal-title":"MedComm"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1093\/carcin\/bgaa083","article-title":"Methylation of the CDX2 Promoter in Helicobacter Pylori-Infected Gastric Mucosa Increases with Age and Its Rapid Demethylation in Gastric Tumors Is Associated with Upregulated Gene Expression","volume":"41","author":"Kim","year":"2020","journal-title":"Carcinogenesis"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ansari, S., Gantuya, B., Tuan, V.P., and Yamaoka, Y. (2018). Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082424"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1007\/s00432-011-1044-7","article-title":"The Relationship among PDX1, CDX2, and Mucin Profiles in Gastric Carcinomas; Correlations with Clinicopathologic Parameters","volume":"137","author":"Can","year":"2011","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/1756-9966-31-98","article-title":"Prognostic Significance of Cdx2 Immunohistochemical Expression in Gastric Cancer: A Meta-Analysis of Published Literatures","volume":"31","author":"Wang","year":"2012","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/s41419-020-03070-z","article-title":"GATA6 Promotes Epithelial-Mesenchymal Transition and Metastasis through MUC1\/\u03b2-Catenin Pathway in Cholangiocarcinoma","volume":"11","author":"Deng","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1136\/gutjnl-2013-306596","article-title":"Regulatory Crosstalk between Lineage-Survival Oncogenes KLF5, GATA4 and GATA6 Cooperatively Promotes Gastric Cancer Development","volume":"64","author":"Chia","year":"2015","journal-title":"Gut"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/onc.2017.397","article-title":"Aberrant GATA2 Epigenetic Dysregulation Induces a GATA2\/GATA6 Switch in Human Gastric Cancer","volume":"37","author":"Song","year":"2018","journal-title":"Oncogene"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wu, C.S., Wei, K.L., Chou, J.L., Lu, C.K., Hsieh, C.C., Lin, J.M.J., Deng, Y.F., Hsu, W.T., Wang, H.M.D., and Leung, C.H. (2016). Aberrant JAK\/STAT Signaling Suppresses TFF1 and TFF2 through Epigenetic Silencing of GATA6 in Gastric Cancer. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091467"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12943-024-02069-w","article-title":"Cancer, Metastasis, and the Epigenome","volume":"23","author":"Kiri","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Blanchet, A., Bourgmayer, A., Kurtz, J.E., Mellitzer, G., and Gaiddon, C. (2021). Isoforms of the P53 Family and Gastric Cancer: A M\u00e9nage \u00e0 Trois for an Unfinished Affair. Cancers, 13.","DOI":"10.3390\/cancers13040916"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1080\/10942912.2023.2281257","article-title":"Anticancer Perspectives of Genistein: A Comprehensive Review","volume":"26","author":"Naeem","year":"2023","journal-title":"Int. J. Food Prop."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/jcp.21596","article-title":"Sustained NF-\u039aB Activation Produces a Short-Term Cell Proliferation Block in Conjunction with Repressing Effectors of Cell Cycle Progression Controlled by E2F or FoxM1","volume":"218","author":"Penzo","year":"2009","journal-title":"J. Cell. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.bbagrm.2011.09.004","article-title":"FOXM1: From Cancer Initiation to Progression and Treatment","volume":"1819","author":"Koo","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA) Gene Regul. Mech."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Merjaneh, N., Hajjar, M., Lan, Y.W., Kalinichenko, V.V., and Kalin, T.V. (2024). The Promise of Combination Therapies with FOXM1 Inhibitors for Cancer Treatment. Cancers, 16.","DOI":"10.3390\/cancers16040756"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e180013","DOI":"10.1001\/jamaoncol.2018.0013","article-title":"Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial","volume":"4","author":"Fuchs","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1007\/s10120-019-01034-7","article-title":"A Phase 3 Study of Nivolumab in Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer (ATTRACTION-2): 2-Year Update Data","volume":"23","author":"Chen","year":"2020","journal-title":"Gastric Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/ijc.34486","article-title":"The Interplay of Oncogenic Signaling, Oxidative Stress and Ferroptosis in Cancer","volume":"153","author":"Zeng","year":"2023","journal-title":"Int. J. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10238-023-01260-5","article-title":"Decoding the Regulatory Landscape of LncRNAs as Potential Diagnostic and Prognostic Biomarkers for Gastric and Colorectal Cancers","volume":"24","author":"Vahidi","year":"2024","journal-title":"Clin. Exp. 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