2026-10-14T11:21:08Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33966986 2026-09-22T17:26:06Z category_7 category_12 category_13 category_46 category_734 category_811 category_64 category_106 category_132 portal_5 item_type_3 month_year_09_2026

<p>Meta-analysis and revision sensitivity audit.</p> Yuye Wu (22381971) Guangjie Li (7588865) Lixing Jiang (25091171) Chaohong Zhang (3072666) Huilong Fang (4512496) Haiqing Fan (18158982) Medicine Cell Biology Genetics Immunology Biological Sciences not elsewhere classified Mathematical Sciences not elsewhere classified Cancer Science Policy Infectious Diseases external cohort reproduced cohort transcriptomic study bulk biomarkers may although component assignment 92 ), including 20 &# 8211 00 &# 8211 prespecified heuristic barrier endothelial barrier direction requires prospective spatial restrict immune access section discovery cohort retrospective public multi e4 mutual exclusivity caf )/ tgf spatial discovery public multi e2 barrier section identity direct caf immune exclusion vascular programs urothelial carcinoma universal two translation framework statistically conclusive results identify reproduce e2 quartile e2 projected e2 positively correlated niche architecture generating mechanism exploratory fixed exclusion score examine whether enriched program effects summaries checkpoint resistance 928 ). 009 ). <div><p>Immune checkpoint inhibitors benefit only a subset of patients with urothelial carcinoma, and bulk biomarkers may not capture spatially organized stromal and vascular programs that restrict immune access. We performed a retrospective public multi-cohort transcriptomic study to examine whether a cancer-associated fibroblast (CAF)/TGF-beta/endothelial barrier direction is associated with immune exclusion and checkpoint resistance in bladder cancer. GSE171351 was used for spatial discovery, GSE319536 for external spatial recurrence testing, TCGA-BLCA for prognosis-oriented support, and IMvigor210, GSE176307 and GSE328930/DUTRENEO for treatment-response projection. In the four-section discovery cohort, rank-5 non-negative matrix factorization separated an E2 barrier-enriched program from an E4 hypoxic epithelial program, although component assignment was strongly associated with section identity. The external cohort reproduced the direct CAF/TGF-beta/endothelial barrier direction in 22 of 22 sections but did not reproduce E2/E4 mutual exclusivity: projected E2 and E4 were positively correlated (rho = 0.928). In IMvigor210, top-quartile E2-high tumors showed suggestive, but not statistically conclusive, evidence of anti-PD-L1 non-response after full biologic covariate adjustment (OR=2.57, 95% CI 1.00–6.64, p = 0.051; delta AUC = 0.009). A prespecified heuristic barrier-exclusion score was associated with non-response in exploratory fixed- and random-effects summaries (OR=1.52, 95% CI 1.20–1.92), including a sensitivity analysis excluding GSE328930. These results identify a recurrent barrier direction rather than a universal two-niche architecture and support a hypothesis-generating mechanism-to-translation framework that requires prospective spatial and pathology-level validation.</p></div> 2026-09-22T17:25:44Z Dataset Dataset 10.1371/journal.pone.0358043.t006 https://figshare.com/articles/dataset/_p_Meta-analysis_and_revision_sensitivity_audit_p_/33966986 CC BY 4.0