TCF3 as a multidimensional biomarker:oncogenicity,genomic alterations,and immune landscape in pan-cancer analysis  

作　　者：Huiling Nie Yang Yu Siqi Zhou Yue Xu Xi Chen Xun Qin Zhangyu Liu Jiayu Huang Hailiang Zhang Jin Yao Qin Jiang Bingbing Wei Xiaojian Qin 

机构地区：[1]The Affiliated Eye Hospital and the Fourth School of Clinical Medicine,Nanjing Medical University,Nanjing 210004,China [2]Department of Urology,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China [3]Department of Ophthalmology,the Fourth Affiliated Hospital of Soochow University,Suzhou 215002,China [4]Department of Urology,the Affiliated Wuxi People’s Hospital of Nanjing Medical University,Wuxi 214023,China

出　　处：《Acta Biochimica et Biophysica Sinica》2025年第2期195-208,共14页生物化学与生物物理学报(英文版)

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.82171074,81970809 and 81570859);the Suzhou Medical Innovation Application Research Project(No.SZM2023027).

摘　　要：Transcription factor 3(TCF3),a pivotal member of the TCF/LEF family,plays a critical role in tumorigenesis.Nonetheless,its impact on the tumor microenvironment(TME)and cancer phenotypes remains elusive.We perform an exhaustive analysis of TCF3 expression,DNA variation profiles,prognostic implications,and associations with the TME and immunological aspects.This study is based on a large-scale pan-cancer cohort,encompassing over 17,000 cancer patients from multiple independent datasets,validated by in vitro assays.Our results show that TCF3/4/7 exhibits differential expression patterns between normal and tumor tissues across pan-cancer analyses.Mutational analysis of TCF3 across diverse cancer types reveals the highest alteration rates in biliary tract cancer.Additionally,mutations and single nucleotide variants in TCF3/4/7 are found to exert varied effects on patient prognosis.Importantly,TCF3 emerges as a robust predictor of survival across all cancer cohorts and among patients receiving immune checkpoint inhibitors.Elevated TCF3 expression is correlated with more aggressive cancer subtypes,as validated by immunohistochemistry and diverse cohort data.Furthermore,TCF3 expression is positively correlated with intratumoral heterogeneity and angiogenesis.In vitro investigations demonstrate that TCF3 is involved in epithelial-mesenchymal transition,migration,invasion,and angiogenesis.These effects are likely mediated through the interaction of TCF3 with the NF-κB/MMP2 pathway,which is modulated by IL-17A in human uveal melanoma MUM2B cells.This study elucidates,for the first time,the significant associations of TCF3 with DNA variation profiles,prognostic outcomes,and the TME in multiple cancer contexts.TCF3 holds promise as a molecular marker for diagnosis and as a potential target for novel therapeutic strategies,particularly in uveal melanoma.

关 键 词：TCF/LEF family TCF3 pan-cancer analysis prognosis tumor microenvironment(TME) epithelial-mesenchymal transition(EMT) 

分 类 号：R73[医药卫生—肿瘤]