{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:02:18Z","timestamp":1780038138527,"version":"3.53.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009329","name":"Scientific Research and Technology Development Program of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","award":["AB23026002"],"award-info":[{"award-number":["AB23026002"]}],"id":[{"id":"10.13039\/501100009329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2024GXNSFBA010037"],"award-info":[{"award-number":["2024GXNSFBA010037"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2023GXNSFAA026229"],"award-info":[{"award-number":["2023GXNSFAA026229"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2023JJB140553"],"award-info":[{"award-number":["2023JJB140553"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2025JJA141112)"],"award-info":[{"award-number":["2025JJA141112)"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303316"],"award-info":[{"award-number":["82303316"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The progression, recurrence, and metastasis of muscle-invasive bladder cancer (MIBC) are closely associated with vasculogenic mimicry (VM). Establishing a VM-based molecular subtyping system and clarifying its regulatory network are essential to overcome current therapeutic limitations in MIBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study collected 1,489 previously reported VM-related genes and identified differentially expressed genes between tumor cells and endothelial cells using single-cell transcriptomic analysis. The intersection of these gene sets yielded VM-related genes, of which 12 were selected to construct a prognostic model validated by multi-omics data, including bulk transcriptomic, genomic, mass cytometry, spatial transcriptomic, and metabolomic datasets. Single-cell and bulk RNA sequencing data were integrated to develop a VM-based molecular subtyping system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MIBC patients were classified into three subtypes: VM, Mixed-VM, and Non-VM, each showing distinct prognostic outcomes consistently validated across multiple independent cohorts. The VM subtype demonstrated the most aggressive clinical behavior, characterized by high cellular plasticity and extensive metabolic reprogramming. Compared to the Non-VM subtype, VM-subtype patients exhibited an immunosuppressive tumor microenvironment and elevated tumor mutational burden (TMB), indicating a potentially favorable response to immunotherapy. Combined treatment with the MEK inhibitor TAK-733 and immune checkpoint inhibitors was proposed as a promising therapeutic strategy for this subgroup.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This novel VM-based molecular subtyping system for MIBC shows strong potential for clinical application in prognosis prediction, immunotherapy response evaluation, and targeted drug discovery, providing a framework to guide personalized treatment strategies for MIBC patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1796762","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:08:47Z","timestamp":1780034927000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A vasculogenic mimicry subtype unveiled by integrated multi-omics predicts prognosis and guides immunotherapy in MIBC"],"prefix":"10.3389","volume":"6","author":[{"given":"Luqing","family":"Wei","sequence":"first","affiliation":[{"name":"School of Information and Management, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhen","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Information and Management, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Feng","sequence":"additional","affiliation":[{"name":"Center for Genomic and Personalized Medicine, Guangxi Medical University","place":["Nanning, China"]},{"name":"Department of Urology, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]},{"name":"The Academician Workstation on Metabolism and Health, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyou","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Collaborative Innovation, University of Macau","place":["Macau, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Computer Engineering, University of California","place":["Irvine, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Tao","sequence":"additional","affiliation":[{"name":"Center for Genomic and Personalized Medicine, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center for Genomic and Personalized Medicine, Guangxi Medical University","place":["Nanning, China"]},{"name":"Department of Urology, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]},{"name":"The Academician Workstation on Metabolism and Health, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Genomic and Personalized Medicine, Guangxi Medical University","place":["Nanning, China"]},{"name":"Department of Urology, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]},{"name":"The Academician Workstation on Metabolism and Health, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zezu","family":"Qin","sequence":"additional","affiliation":[{"name":"Center for Genomic and Personalized Medicine, Guangxi Medical University","place":["Nanning, China"]},{"name":"Department of Urology, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]},{"name":"The Academician Workstation on Metabolism and Health, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuancheng","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Genomic and Personalized Medicine, Guangxi Medical University","place":["Nanning, China"]},{"name":"Department of Urology, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]},{"name":"The Academician Workstation on Metabolism and Health, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenkun","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Information and Management, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Information and Management, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Information and Management, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Genomic and Personalized Medicine, Guangxi Medical University","place":["Nanning, China"]},{"name":"Department of Urology, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]},{"name":"The Academician Workstation on Metabolism and Health, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Feng","sequence":"additional","affiliation":[{"name":"Center for Genomic and Personalized Medicine, Guangxi Medical University","place":["Nanning, China"]},{"name":"The Academician Workstation on Metabolism and Health, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Genomic and Personalized Medicine, Guangxi Medical University","place":["Nanning, China"]},{"name":"The Academician Workstation on Metabolism and Health, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Information and Management, Guangxi Medical University","place":["Nanning, China"]},{"name":"School of Humanities and Social Sciences, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e1005112","DOI":"10.1371\/journal.pcbi.1005112","article-title":"Cytofkit: a bioconductor package for an integrated mass cytometry data analysis pipeline","volume":"12","author":"Chen","year":"2016","journal-title":"PLoS Comput. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5077","DOI":"10.1038\/s41467-020-18916-5","article-title":"Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma","volume":"11","author":"Chen","year":"2020","journal-title":"Nat. Commun."},{"key":"B3","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/s41572-023-00468-9","article-title":"Bladder cancer","volume":"9","author":"Dyrskjot","year":"2023","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B4","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1080\/00365513.2023.2286645","article-title":"Plasma or serum 5-hydroxyindoleacetic acid can be used interchangeably in patients with neuroendocrine tumours","volume":"83","author":"Ewang-Emukowhate","year":"2023","journal-title":"Scand. J. Clin. Lab. Invest"},{"key":"B5","doi-asserted-by":"publisher","first-page":"695662","DOI":"10.3389\/fgene.2021.695662","article-title":"Integrative transcriptomic, lipidomic, and metabolomic analysis reveals potential biomarkers of basal and luminal muscle invasive bladder cancer subtypes","volume":"12","author":"Feng","year":"","journal-title":"Front. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"5440","DOI":"10.3390\/cancers13215440","article-title":"Single-cell proteomic analysis dissects the complexity of tumor microenvironment in muscle invasive bladder cancer","volume":"13","author":"Feng","year":"","journal-title":"Cancers (Basel)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1016\/s0140-6736(55)93160-3","article-title":"Determination of 5-hydroxy-indole-acetic acid in urine; and its excretion in patients with malignant carcinoids","volume":"269","author":"Hanson","year":"1955","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nrc1092","article-title":"Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma","volume":"3","author":"Hendrix","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"6147","DOI":"10.21873\/anticanres.12967","article-title":"TAK-733, a selective MEK inhibitor, enhances voreloxin-induced apoptosis in myeloid leukemia cells","volume":"38","author":"Jasek-Gajda","year":"2018","journal-title":"Anticancer Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"42183","DOI":"10.18632\/oncotarget.5619","article-title":"Mutant HRAS as novel target for MEK and mTOR inhibitors","volume":"6","author":"Kiessling","year":"2015","journal-title":"Oncotarget"},{"key":"B11","doi-asserted-by":"publisher","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":"B12","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1126\/science.1132939","article-title":"The connectivity map: using gene-expression signatures to connect small molecules, genes, and disease","volume":"313","author":"Lamb","year":"2006","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinforma."},{"key":"B14","doi-asserted-by":"publisher","first-page":"62","DOI":"10.17116\/patol20238506162","article-title":"Vasculogenic mimicry","volume":"85","author":"Lapkina","year":"2023","journal-title":"Arkh Patol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1001\/jama.2020.17598","article-title":"Bladder cancer: a review","volume":"324","author":"Lenis","year":"2020","journal-title":"JAMA"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1202656","DOI":"10.3389\/fonc.2023.1202656","article-title":"Therapeutic potential of vasculogenic mimicry in urological tumors","volume":"13","author":"Lin","year":"2023","journal-title":"Front. Oncol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"W159","DOI":"10.1093\/nar\/gkac394","article-title":"CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting","volume":"50","author":"Liu","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"217731","DOI":"10.1016\/j.canlet.2025.217731","article-title":"COL1A1-positive endothelial cells promote gastric cancer progression via the ANGPTL4-SDC4 axis driven by endothelial-to-mesenchymal transition","volume":"623","author":"Liu","year":"2025","journal-title":"Cancer Lett."},{"key":"B19","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13045-020-00858-6","article-title":"Vasculogenic mimicry in carcinogenesis and clinical applications","volume":"13","author":"Luo","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"bbab260","DOI":"10.1093\/bib\/bbab260","article-title":"oncoPredict: an R package for predicting in vivo or cancer patient drug response and biomarkers from cell line screening data","volume":"22","author":"Maeser","year":"2021","journal-title":"Brief. Bioinform"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1101\/gr.239244.118","article-title":"Maftools: efficient and comprehensive analysis of somatic variants in cancer","volume":"28","author":"Mayakonda","year":"2018","journal-title":"Genome Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3921","DOI":"10.18632\/oncotarget.27767","article-title":"MEK is a promising target in the basal subtype of bladder cancer","volume":"11","author":"Merrill","year":"2020","journal-title":"Oncotarget"},{"key":"B23","doi-asserted-by":"publisher","first-page":"404","DOI":"10.3322\/caac.21631","article-title":"Treatment of muscle-invasive and advanced bladder cancer in 2020","volume":"70","author":"Patel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"B24","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.annonc.2021.11.012","article-title":"Bladder cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up","volume":"33","author":"Powles","year":"2022","journal-title":"Ann. Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2951","DOI":"10.1038\/onc.2014.249","article-title":"Tumor heterogeneity and plasticity as elusive drivers for resistance to MAPK pathway inhibition in melanoma","volume":"34","author":"Roesch","year":"2015","journal-title":"Oncogene"},{"key":"B26","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/s41467-023-36062-6","article-title":"Estimation of cell lineages in tumors from spatial transcriptomics data","volume":"14","author":"Ru","year":"2023","journal-title":"Nat. Commun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"120022","DOI":"10.1016\/j.cca.2024.120022","article-title":"UPLC-Q-TOF\/MS-based urine metabolomics for the diagnosis and staging of bladder cancer","volume":"565","author":"Shi","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"B28","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2025.01.22.634215","DOI":"10.1101\/2025.01.22.634215","article-title":"Adaptive plasticity tumor cells modulate MAPK-targeting therapy response in colorectal cancer","author":"Villarreal","year":"2025","journal-title":"bioRxiv"},{"key":"B30","doi-asserted-by":"publisher","first-page":"53168","DOI":"10.18632\/oncotarget.18230","article-title":"MEK inhibition enhances efficacy of bacillus calmette-guerin on bladder cancer cells by reducing release of toll-like receptor 2-activated antimicrobial peptides","volume":"8","author":"Whang","year":"2017","journal-title":"Oncotarget"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e13115","DOI":"10.1111\/cpr.13115","article-title":"Role of the CCL2-CCR2 signalling axis in cancer: mechanisms and therapeutic targeting","volume":"54","author":"Xu","year":"2021","journal-title":"Cell Prolif."},{"key":"B32","doi-asserted-by":"publisher","first-page":"D955","DOI":"10.1093\/nar\/gks1111","article-title":"Genomics of drug sensitivity in cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells","volume":"41","author":"Yang","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"687975","DOI":"10.3389\/fimmu.2021.687975","article-title":"IOBR: multi-omics immuno-oncology biological research to decode tumor microenvironment and signatures","volume":"12","author":"Zeng","year":"2021","journal-title":"Front. Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"105507","DOI":"10.1016\/j.phrs.2021.105507","article-title":"Regulatory mechanisms and therapeutic targeting of vasculogenic mimicry in hepatocellular carcinoma","volume":"166","author":"Zheng","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e2419540","DOI":"10.1002\/adma.202419540","article-title":"Glycated ECM derived carbon dots inhibit tumor vasculogenic mimicry by disrupting RAGE nuclear translocation and its interaction with HMGB1","volume":"37","author":"Zheng","year":"2025","journal-title":"Adv. Mater"}],"container-title":["Frontiers in Bioinformatics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2026.1796762\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:08:48Z","timestamp":1780034928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2026.1796762\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":35,"alternative-id":["10.3389\/fbinf.2026.1796762"],"URL":"https:\/\/doi.org\/10.3389\/fbinf.2026.1796762","relation":{},"ISSN":["2673-7647"],"issn-type":[{"value":"2673-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1796762"}}