{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T21:40:12Z","timestamp":1769982012024,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Evidence Based Medicine"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Upper tract urothelial carcinoma (UTUC) accounts for about 31% of urothelial malignancies in China, a markedly higher proportion than in Western countries. Limited molecular understanding hampers diagnosis and therapy. This study aimed to explore molecular mechanisms and identify potential biomarkers through a cohort\u2010based integrative multi\u2010omics analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed 48 paired UTUC tumor and adjacent normal tissues. RNA and whole\u2010exome sequencing were performed to explore difference. Weighted gene co\u2010expression network analysis (WGCNA) was used to identify modules and hub genes associated with pathological traits. Validation included survival analysis within the discovery cohort, cross\u2010cancer evaluation using The Cancer Genome Atlas Bladder Urothelial Carcinoma dataset (TCGA\u2010BLCA) via gene expression profiling interactive analysis, and independent confirmation with a UTUC cohort from cBioPortal (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a032). Protein expression was examined using immunohistochemistry (IHC) data from the Human Protein Atlas.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 3968 differentially expressed genes enriched in genitourinary development and calcium signaling pathways. WGCNA revealed four co\u2010expression modules associated with infiltration, with 64 genes linked to pathological traits. Integrative analysis prioritized methionine sulfoxide reductase B3 (MSRB3) and Synaptopodin 2 (SYNPO2) as hub genes. Within the UTUC cohort, both genes showed trends toward poorer progression\u2010free survival; in TCGA\u2010BLCA, their expression and survival patterns provided supportive cross\u2010cancer evidence; and in the independent UTUC dataset, clinicopathological correlations were directionally consistent with the discovery findings. IHC suggested lower protein expression in UTUC compared with normal urothelium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This integrative multi\u2010omics cohort study suggests MSRB3 and SYNPO2 as candidate biomarkers for UTUC progression, offering insights for risk stratification and potential therapeutic development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jebm.70093","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T07:29:10Z","timestamp":1765870150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dissecting Genetic Mechanisms of UTUC: A Network\u2010Based Multi\u2010Omics Cohort Study"],"prefix":"10.1111","volume":"18","author":[{"given":"Tingting","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Urology, Lab of Health Data Science, Innovation Institute for Integration of Medicine and Engineering Frontiers Science Center for Disease\u2010Related Molecular Network West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Bio\u2010Resource and Eco\u2010Environment of Ministry of Education, College of Life Sciences Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banghua","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Urology, Lab of Health Data Science, Innovation Institute for Integration of Medicine and Engineering West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, Lab of Health Data Science, Innovation Institute for Integration of Medicine and Engineering West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meilin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Urology, Lab of Health Data Science, Innovation Institute for Integration of Medicine and Engineering West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuedan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Lab of Health Data Science, Innovation Institute for Integration of Medicine and Engineering West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Lab of Health Data Science, Innovation Institute for Integration of Medicine and Engineering Frontiers Science Center for Disease\u2010Related Molecular Network West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanyan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Urology, Lab of Health Data Science, Innovation Institute for Integration of Medicine and Engineering Frontiers Science Center for Disease\u2010Related Molecular Network West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Lab of Health Data Science, Innovation Institute for Integration of Medicine and Engineering Frontiers Science Center for Disease\u2010Related Molecular Network West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Bio\u2010Resource and Eco\u2010Environment of Ministry of Education, College of Life Sciences Sichuan University  Chengdu Sichuan 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