{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:57:46Z","timestamp":1791910666955,"version":"4.3.4"},"reference-count":91,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The human genome has a profound impact on human health and disease detection. Carcinoma (cancer) is one of the prominent diseases that majorly affect human health and requires the development of different treatment strategies and targeted therapies based on effective disease detection. Therefore, our research aims to identify biomarkers associated with distinct cancer types (gastric, lung, and breast) using machine learning. In the current study, we have analyzed the human genomic data of gastric cancer, breast cancer, and lung cancer patients using XGB-BIF (i.e., XGBoost-Driven Biomarker Identification Framework for detecting cancer). The proposed framework utilizes feature selection via XGBoost (eXtreme Gradient Boosting), which captures feature interactions efficiently and takes care of the non-linear effects in the genomic data. The research progressed by training XGBoost on the full dataset, ranking the features based on the Gain measure (importance), followed by the classification phase, which employed support vector machines (SVM), logistic regression (LR), and random forest (RF) models for classifying cancer-diseased and non-diseased states. To ensure interpretability and transparency, we also applied SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME), enabling the identification of high-impact biomarkers contributing to risk stratification. Biomarker significance is discussed primarily via pathway enrichment and by studying survival analysis (Kaplan\u2013Meier curves, Cox regression) for identified biomarkers to strengthen translational value. Our models achieved high predictive performance, with an accuracy of more than 90%, to classify and link genomic data into diseased (cancer) and non-diseased states. Furthermore, we evaluated the models using Cohen\u2019s Kappa statistic, which confirmed strong agreement between predicted and actual risk categories, with Kappa scores ranging from 0.80 to 0.99. Our proposed framework also achieved strong predictions on the METABRIC dataset during external validation, attaining an AUC-ROC of 93%, accuracy of 0.79%, and Kappa of 74%. Through extensive experimentation, XGB-BIF identified the top biomarker genes for different cancer datasets (gastric, lung, and breast). CBX2, CLDN1, SDC2, PGF, FOXS1, ADAMTS18, POLR1B, and PYCR3 were identified as important biomarkers to identify diseased and non-diseased states of gastric cancer; CAVIN2, ADAMTS5, SCARA5, CD300LG, and GIPC2 were identified as important biomarkers for breast cancer; and CLDN18, MYBL2, ASPA, AQP4, FOLR1, and SLC39A8 were identified as important biomarkers for lung cancer. XGB-BIF could be utilized for identifying biomarkers of different cancer types using genetic data, which can further help clinicians in developing targeted therapies for cancer patients.<\/jats:p>","DOI":"10.3390\/ijms26125590","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T08:18:06Z","timestamp":1749629886000},"page":"5590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["XGB-BIF: An XGBoost-Driven Biomarker Identification Framework for Detecting Cancer Using Human Genomic Data"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6595-171X","authenticated-orcid":false,"given":"Veena","family":"Ghuriani","sequence":"first","affiliation":[{"name":"Maitreyi College, University of Delhi, New Delhi 110021, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotsna Talreja","family":"Wassan","sequence":"additional","affiliation":[{"name":"Maitreyi College, University of Delhi, New Delhi 110021, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyal","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Maitreyi College, University of Delhi, New Delhi 110021, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshika","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Maitreyi College, University of Delhi, New Delhi 110021, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"D\u2019Argenio, V., Dittfeld, L., Lazzeri, P., Tomaiuolo, R., and Tasciotti, E. (2021). Unraveling the Balance between Genes, Microbes, Lifestyle and the Environment to Improve Healthy Reproduction. Genes, 12.","DOI":"10.3390\/genes12040605"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/nrg3373","article-title":"Phenotypic impact of genomic structural variation: Insights from and for human disease","volume":"14","author":"Weischenfeldt","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nrg1767","article-title":"Structural variation in the human genome","volume":"7","author":"Feuk","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1097\/CM9.0000000000001474","article-title":"Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020","volume":"134","author":"Cao","year":"2021","journal-title":"Chin. Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"395","DOI":"10.5603\/NJO.2015.0077","article-title":"Lung cancer, the leading cause of cancer deaths among women in Europe","volume":"65","author":"Sulkowska","year":"2015","journal-title":"Nowotwory. J. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.3748\/wjg.v29.i16.2452","article-title":"Updates on global epidemiology, risk and prognostic factors of gastric cancer","volume":"29","author":"Yang","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s12013-014-0459-6","article-title":"Breast Cancer: Epidemiology and Etiology","volume":"72","author":"Tao","year":"2015","journal-title":"Cell Biochem. Biophys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s40495-017-0088-z","article-title":"Environmental Influences in the Etiology of Colorectal Cancer: The Premise of Metabolomics","volume":"3","author":"Rattray","year":"2017","journal-title":"Curr. Pharmacol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10549-011-1518-y","article-title":"Mutational characterization of individual breast tumors: TP53 and PI3K pathway genes are frequently and distinctively mutated in different subtypes","volume":"132","author":"Boyault","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Testa, U., Castelli, G., and Pelosi, E. (2018). Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells. Cancers, 10.","DOI":"10.3390\/cancers10080248"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/s41568-019-0179-8","article-title":"Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy","volume":"19","author":"Skoulidis","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.resinv.2021.10.008","article-title":"Small cell lung cancer; recent advances of its biology and therapeutic perspective","volume":"60","author":"Hayashi","year":"2022","journal-title":"Respir. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, R.C., and Wang, Z. (2023). Precision Medicine: Disease Subtyping and Tailored Treatment. Cancers, 15.","DOI":"10.3390\/cancers15153837"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3322\/caac.20128","article-title":"Genetics, genomics, and cancer risk assessment: State of the Art and Future Directions in the Era of Personalized Medicine","volume":"61","author":"Weitzel","year":"2011","journal-title":"CA A Cancer J. Clin."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nagaraj, A. (2023). COVID-19\u2014Monitoring with IoT Devices, Bentham Science Publishers.","DOI":"10.2174\/97898151794531230101"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, Z., Gao, X., Zeng, R., Wu, Q., Sun, H., Wu, W., Zhang, X., Sun, G., Yan, B., and Wu, L. (2020). Changes of the Gastric Mucosal Microbiome Associated with Histological Stages of Gastric Carcinogenesis. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00997"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6633","DOI":"10.1128\/AEM.01437-16","article-title":"Effects of Proton Pump Inhibitors on the Gastric Mucosa-Associated Microbiota in Dyspeptic Patients","volume":"82","author":"Sterbini","year":"2016","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1109\/TPAMI.2020.3031898","article-title":"Small Data Challenges in Big Data Era: A Survey of Recent Progress on Unsupervised and Semi-Supervised Methods","volume":"44","author":"Qi","year":"2020","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.7150\/ijbs.84331","article-title":"SDC2 Stabilization by USP14 Promotes Gastric Cancer Progression through Co-option of PDK1","volume":"19","author":"You","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.18632\/oncotarget.2936","article-title":"Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikis in gastric cancer","volume":"6","author":"Huang","year":"2014","journal-title":"Oncotarget"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yang, Y., Zufu, J., Weizhou, W., Libin, R., Chengyang, Y., Yuning, X., Liling, W., Kunpeng, W., Jinggang, M., and Shankun, Z. (2021). Chronic Hepatitis Virus Infection Are Associated with High Risk of Gastric Cancer: A Systematic Review and Cumulative Analysis. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.703558"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1631\/jzus.B1400077","article-title":"Epigenetic regulation by polycomb group complexes: Focus on roles of CBX proteins","volume":"15","author":"Ma","year":"2014","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Morgos, D.-T., Stefani, C., Miricescu, D., Greabu, M., Stanciu, S., Nica, S., Stanescu, S., Balan, D.G., Balcangiu, S., and Coculescu, E.C. (2024). Targeting PI3K\/AKT\/mTOR and MAPK Signaling Pathways in Gastric Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031848"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.2147\/OTT.S126424","article-title":"Mechanism of immune evasion in breast cancer","volume":"10","author":"Wang","year":"2017","journal-title":"OncoTargets Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4325105","DOI":"10.1155\/2019\/4325105","article-title":"DNA Repair Deficiency in Breast Cancer: Opportunities for Immunotherapy","volume":"2019","author":"Gilmore","year":"2019","journal-title":"J. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/bcr3103","article-title":"Initiating breast cancer by PIK3CA mutation","volume":"14","author":"Miller","year":"2012","journal-title":"Breast Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1007\/s10115-023-02010-5","article-title":"Feature selection techniques for machine learning: A survey of more than two decades of research","volume":"66","author":"Theng","year":"2024","journal-title":"Knowl. Inf. Syst."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Muthukrishnan, R., and Rohini, R. (2016, January 24). LASSO: A Feature Selection Technique in Predictive Modeling for Machine Learning. Proceedings of the 2016 IEEE International Conference on Advances in Computer Applications (ICACA), Coimbatore, India.","DOI":"10.1109\/ICACA.2016.7887916"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4018\/IJISMD.2021040102","article-title":"A Hybrid Approach for Feature Selection Based on Genetic Algorithm and Recursive Feature Elimination","volume":"12","author":"Rani","year":"2021","journal-title":"Int. J. Inf. Syst. Model. Des."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature10983","article-title":"The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups","volume":"486","author":"Curtis","year":"2012","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Eftang, L.L., Esbensen, Y., Tann\u00e6s, T.M., Blom, G.P., Bukholm, I.R., and Bukholm, G. (2013). Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-586"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nied\u017awiedzka-Rystwej, P., Grywalska, E., Hrynkiewicz, R., Wo\u0142\u0105cewicz, M., Becht, R., and Roli\u0144ski, J. (2020). The Double-Edged Sword Role of Viruses in Gastric Cancer. Cancers, 12.","DOI":"10.3390\/cancers12061680"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sekhar, V., Pollicino, T., Diaz, G., Engle, R.E., Alayli, F., Melis, M., Kabat, J., Tice, A., Pomerenke, A., and Altan-Bonnet, N. (2018). Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006916"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bhat, A.A., Syed, N., Therachiyil, L., Nisar, S., Hashem, S., Macha, M.A., Yadav, S.K., Krishnankutty, R., Muralitharan, S., and Al-Naemi, H. (2020). Claudin-1, A Double-Edged Sword in Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020569"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gong, Y., Jin, X., Yuan, B., Lv, Y., Yan, G., Liu, M., Xie, C., Liu, J., Tang, Y., and Gao, H. (2021). G Protein-Coupled Receptor 109A Maintains the Intestinal Integrity and Protects Against ETEC Mucosal Infection by Promoting IgA Secretion. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.583652"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Menter, D.G., and DuBois, R.N. (2012). Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion. Int. J. Cell Biol., 2012.","DOI":"10.1155\/2012\/723419"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.2353\/ajpath.2010.100172","article-title":"Phosphorylation of Focal Adhesion Kinase at Tyr397 in Gastric Carcinomas and its Clinical Significance","volume":"177","author":"Lai","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8057","DOI":"10.18632\/oncotarget.14074","article-title":"Low expression of Rap1GAP is associated with epithelial-mesenchymal transition (EMT) and poor prognosis in gastric cancer","volume":"8","author":"Yang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/0016-5085(87)90264-2","article-title":"Frequent overexpression, but not activation by point mutation, of ras genes in primary human gastric cancers","volume":"93","author":"Fujita","year":"1987","journal-title":"Gastroenterology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Magnelli, L., Schiavone, N., Staderini, F., Biagioni, A., and Papucci, L. (2020). MAP Kinases Pathways in Gastric Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082893"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.3390\/cancers6031441","article-title":"The Role of PI3K\/Akt\/mTOR Signaling in Gastric Carcinoma","volume":"6","author":"Matsuoka","year":"2014","journal-title":"Cancers"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"176","DOI":"10.7150\/jca.90008","article-title":"Receptor-interacting protein kinase 2 is associated with tumor immune infiltration, immunotherapy-related biomarkers, and affects gastric cancer cells growth in vivo","volume":"15","author":"Yang","year":"2024","journal-title":"J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Yang, Q., Tian, S., Liu, Z., and Dong, W. (2021). Knockdown of RIPK2 Inhibits Proliferation and Migration, and Induces Apoptosis via the NF-\u03baB Signaling Pathway in Gastric Cancer. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.627464"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Yu, S., and Zhang, W. (2023). NOD-like Receptor Signaling Pathway in Gastrointestinal Inflammatory Diseases and Cancers. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914511"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nri3565","article-title":"NOD proteins: Regulators of inflammation in health and disease","volume":"14","author":"Philpott","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Negroni, A., Colantoni, E., Cucchiara, S., and Stronati, L. (2020). Necroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives. Biomolecules, 10.","DOI":"10.20944\/preprints202009.0084.v1"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"152756","DOI":"10.1016\/j.prp.2019.152756","article-title":"Relationship between SDC1 and cadherin signalling activation in cancer","volume":"216","author":"Liao","year":"2020","journal-title":"Pathol.-Res. Pract."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"110658","DOI":"10.1016\/j.intimp.2023.110658","article-title":"The immunity modulation of transforming growth factor-\u03b2 in malaria and other pathological process","volume":"122","author":"Wu","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, R., Song, B., Hong, X., Shen, Z., Sui, L., and Wang, S. (2020). microRNA-9 Inhibits Vulnerable Plaque Formation and Vascular Remodeling via Suppression of the SDC2-Dependent FAK\/ERK Signaling Pathway in Mice with Atherosclerosis. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00804"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"De Pasquale, V., and Pavone, L.M. (2020). Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186588"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Hashimoto, I., and Oshima, T. (2022). Claudins and Gastric Cancer: An Overview. Cancers, 14.","DOI":"10.3390\/cancers14020290"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41420-024-01957-w","article-title":"RIPK3 signaling and its role in regulated cell death and diseases","volume":"10","author":"Zhou","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Xu, X., Guo, Y., Liu, M., Hu, Y., and Li, S. (2024). Advancements in the clinical application of gene methylation for early cancer detection. Front. Epigenet. Epigenom., 2.","DOI":"10.3389\/freae.2024.1430294"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Souza, M.C., Nunes, S., Figuer\u00eado, S.H.S., de Almeida, B.S., Santos, I.P.C., Cassali, G.D., Arruda, S.M., Cardoso, T.M.S., Estrela-Lima, A., and Damasceno, K.A. (2024). Versican Proteolysis by ADAMTS: Understanding Versikine Expression in Canine Spontaneous Mammary Carcinomas. Cancers, 16.","DOI":"10.3390\/cancers16234057"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mou, K., Wang, H., Zhu, S., Luo, J., Wang, J., Peng, L., Lei, Y., Zhang, Y., Huang, S., and Zhao, H. (2024). Comprehensive analysis of the prognostic and immunological role of cavins in non-small cell lung cancer. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-13280-9"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/s41374-021-00699-y","article-title":"Matrix Metalloproteinase 11 (MMP11) in Macrophages Promotes the Migration of HER2-Positive Breast Cancer Cells and Monocyte Recruitment through CCL2\u2013CCR2 Signaling","volume":"102","author":"Kang","year":"2022","journal-title":"Lab. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11010-017-3055-4","article-title":"SCARA5 Plays a Critical Role in the Progression and Metastasis of Breast Cancer by Inactivating the ERK1\/2, STAT3, and AKT Signaling Pathways","volume":"435","author":"You","year":"2017","journal-title":"Mol. Cell. Biochem."},{"key":"ref_58","first-page":"91","article-title":"Early growth response 1 transcription factor and its context-dependent functions in glioblastoma","volume":"28","author":"Rasras","year":"2024","journal-title":"Contemp. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"13716","DOI":"10.18632\/oncotarget.14627","article-title":"Cleavage of Fibulin-2 by the aggrecanases ADAMTS-4 and ADAMTS-5 contributes to the tumorigenic potential of breast cancer cells","volume":"8","author":"Fontanil","year":"2017","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Han, Q., Qiu, S., Hu, H., Li, W., and Li, X. (2023). Role of Caveolae family-related proteins in the development of breast cancer. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1242426"},{"key":"ref_61","first-page":"639","article-title":"MMP-11 as a biomarker for metastatic breast cancer by immunohistochemical-assisted imaging mass spectrometry","volume":"411","author":"Clases","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_62","unstructured":"(2025, May 30). SCARA5 Scavenger Receptor Class A Member 5. National Center of Biotechnology Information, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/?term=286133."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ni, Q., Li, X., Huang, H., and Ge, Z. (2023). Decreased expression of SCARA5 predicts a poor prognosis in melanoma using bioinformatics analysis. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1015358"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1080\/07357907.2018.1533965","article-title":"Tumor suppression by the EGR1, DMP1, ARF, p53, and PTEN Network","volume":"36","author":"Inoue","year":"2018","journal-title":"Cancer Investig."},{"key":"ref_65","unstructured":"(2025, May 30). EGR1 Early Growth Response 1. National Center of Biotechnology Information, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene?Cmd=DetailsSearch&Db=gene&Term=1958&utm_source=chatgpt.com."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hansson, M.L., Behmer, S., Ceder, R., Mohammadi, S., Preta, G., Grafstr\u00f6m, R.C., Fadeel, B., and Wallberg, A.E. (2012). MAML1 Acts Cooperatively with EGR1 to Activate EGR1-Regulated Promoters: Implications for Nephrogenesis and the Development of Renal Cancer. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046001"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s00109-016-1403-6","article-title":"Egr-1 deficiency protects from renal inflammation and fibrosis","volume":"94","author":"Ho","year":"2016","journal-title":"J. Mol. Med."},{"key":"ref_68","unstructured":"Xie, H. (2020). The Epigenetic Role of EGR1 During Postnatal Brain Development and in Neuronal Activity. [Ph.D. Thesis, Virginia Polytechnic Institute and State University]. Available online: https:\/\/grantome.com\/grant\/NIH\/R01-NS094574-05?utm_source=chatgpt.com."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"96865","DOI":"10.18632\/oncotarget.18292","article-title":"EGR1 regulates cellular metabolism and survival in endocrine resistant breast cancer","volume":"8","author":"Boca","year":"2017","journal-title":"Oncotarget"},{"key":"ref_70","first-page":"75","article-title":"Aquaporin 1 and aquaporin 4 are involved in invasion of lung cancer cells","volume":"58","author":"Xie","year":"2012","journal-title":"Clin. Lab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12964-023-01116-1","article-title":"Amino acid metabolism regulated by lncRNAs: The propellant behind cancer metabolic reprogramming","volume":"21","author":"Hu","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8643","DOI":"10.1074\/jbc.M709824200","article-title":"Correlation of the Tight Junction-like Distribution of Claudin-1 to the Cellular Tropism of Hepatitis C Virus","volume":"283","author":"Yang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_73","first-page":"126","article-title":"Tight junctions in lung cancer and lung metastasis: A review","volume":"5","author":"Soini","year":"2012","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6022","DOI":"10.1111\/j.1742-4658.2008.06731.x","article-title":"Invasion of enteropathogenic Escherichia coli into host cells through epithelial tight junctions","volume":"275","author":"Li","year":"2008","journal-title":"FEBS J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"20166","DOI":"10.18632\/oncotarget.7737","article-title":"Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome","volume":"7","author":"Walter","year":"2016","journal-title":"Oncotarget"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"104122","DOI":"10.1016\/j.jprot.2021.104122","article-title":"Identification of proteins related with pemetrexed resistance by iTRAQ and PRM-based comparative proteomic analysis and exploration of IGF2BP2 and FOLR1 functions in non-small cell lung cancer cells","volume":"237","author":"Han","year":"2021","journal-title":"J. Proteom."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.tem.2021.12.003","article-title":"Emerging roles for folate receptor FOLR1 in signaling and cancer","volume":"33","author":"Nawaz","year":"2022","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ahmed, F. (2019). Integrated Network Analysis Reveals FOXM1 and MYBL2 as Key Regulators of Cell Proliferation in Non-small Cell Lung Cancer. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.01011"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40246-019-0233-3","article-title":"SLC39A8 gene encoding a metal ion transporter: Discovery and bench to bedside","volume":"13","author":"Nebert","year":"2019","journal-title":"Hum. Genom."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.7150\/jca.98829","article-title":"Important functions and molecular mechanisms of aquaporins family on respiratory diseases: Potential translational values","volume":"15","author":"Li","year":"2024","journal-title":"J. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Lin, G., Chen, L., Lin, L., Lin, H., Guo, Z., Xu, Y., Hu, C., Fu, J., Lin, Q., and Chen, W. (2021). Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.736367"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Han, Y., Wang, X., Xu, M., Teng, Z., Qin, R., Tan, G., Li, P., Sun, P., Liu, H., and Chen, L. (2023). Aspartoacylase promotes the process of tumour development and is associated with immune infiltrates in gastric cancer. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11088-7"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"154068","DOI":"10.1016\/j.prp.2022.154068","article-title":"Expression and prognostic analysis of CLDN18 and Claudin18.2 in lung adenocarcinoma","volume":"238","author":"Liu","year":"2022","journal-title":"Pathol.-Res. Pract."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"121802","DOI":"10.1016\/j.lfs.2023.121802","article-title":"Recent advances in using folate receptor 1 (FOLR1) for cancer diagnosis and treatment, with an emphasis on cancers that affect women","volume":"326","author":"Varaganti","year":"2023","journal-title":"Life Sci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Lee, Y., Wu, Z., Yang, S., Schreiner, S.M., Gonzalez-Smith, L.D., and Rhie, S.K. (2022). Characterizing and Targeting Genes Regulated by Transcription Factor MYBL2 in Lung Adenocarcinoma Cells. Cancers, 14.","DOI":"10.3390\/cancers14204979"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.18632\/aging.202452","article-title":"Evaluation of the prognostic values of solute carrier (SLC) family 39 genes for patients with lung adenocarcinoma","volume":"13","author":"Zhou","year":"2021","journal-title":"Aging"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-3-031-04083-2_2","article-title":"Explainable AI Methods\u2014A Brief Overview","volume":"Volume 13200","author":"Holzinger","year":"2022","journal-title":"xxAI-Beyond Explainable AI"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Parmigiani, G., and Johnson, W.E. (2020). ComBat-seq: Batch effect adjustment for RNA-seq count data. NAR Genom. Bioinform., 2.","DOI":"10.1093\/nargab\/lqaa078"},{"key":"ref_89","unstructured":"(2025, May 30). GEO Accession Viewer, Available online: https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE184336."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Silhavy, R., and Silhavy, P. (2023). A Review of Evaluation Metrics in Machine Learning Algorithms. Artificial Intelligence Application in Networks and Systems, Proceedings of the 12th Computer Science Online Conference 2023, Online, 3\u20135 April 2023, Springer.","DOI":"10.1007\/978-3-031-35314-7"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1213\/ANE.0000000000005358","article-title":"Kaplan-Meier curves, log-rank tests, and cox regression for time-to-event data","volume":"132","author":"Schober","year":"2021","journal-title":"Anesth. Analg."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:50:05Z","timestamp":1760032205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":91,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125590"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125590","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]}}}