A pan-cancer analysis of the oncogenic role of transcription factor 3 in human tumors

CHEN Yawen; GAO Yunhe; ZHAO Xudong; ZHAO Yunshan

doi:10.3969/j.issn.1009-0460.2025.05.011

Abstract：Objective To investigate the prognostic and immunological roles of transcription factor 3(TCF3)across pan-cancer.Methods Using multi-omics datasets from the cancer genome atlas(TCGA),gene expression omnibus(GEO),human protein atlas(HPA),and bioinformatics tools,we analyzed TCF3 expression and its associations with prognosis,immune infiltration,and molecular features in 33 cancer types.Results TIMER database analysis found that the mRNA levels of TCF3 in bladder urothelial carcinoma,breast invasive carcinoma,cholangiocarcinoma,colon adenocarcinoma,esophageal cancer,and glioblastoma multiforme were significantly higher than those in adjacent normal tissues(P<0.05).However,TCF3 mRNA was significantly reduced only in melanoma of the skin(P<0.05).High TCF3 expression was significantly associated with worse overall survival(OS)in adrenocortical carcinoma(HR=2.3,P<0.001),clear cell renal cell carcinoma(HR=1.4,P=0.040),hepatocellular carcinoma(HR=1.7,P=0.002),mesothelioma(HR=3.1,P<0.001),prostate adenocarcinoma(HR=1.3,P=0.033),and sarcoma(HR=1.6,P=0.006).Conversely,low TCF3 expression correlated with poor OS in thymoma(HR=0.6,P=0.008)and uterine corpus endometrial carcinoma(HR=0.8,P=0.034).For disease-free survival(DFS),elevated TCF3 predicted adverse outcomes in adrenocortical carcinoma(P<0.001)and uveal melanoma(P=0.005).TCF3 expression also showed significant associations with tumor mutational burden,microsatellite instability,immune cell infiltration(e.g.,fibroblasts and endothelial cells),and phosphorylation levels(P<0.001).Conclusion TCF3 serves as a pan-cancer prognostic and immunomodulatory biomarker,with dual roles in tumor progression depending on cancer type.Its interaction with Wnt signaling and immune microenvironment highlights its potential as a therapeutic target for cancer immunotherapy.