• TCF3/4/7 exhibit differential expression between normal and tumor tissues across multiple cancer types, with TCF3 mutations most frequent in biliary tract cancer.
• Elevated TCF3 expression is a robust predictor of poor survival across all cancer cohorts and among patients receiving immune checkpoint inhibitors.
• TCF3 expression positively correlates with intratumoral heterogeneity and angiogenesis, and in vitro studies show its involvement in EMT, migration, invasion, and angiogenesis via the NF-κB/MMP2 pathway modulated by IL-17A.
• TCF3 is proposed as a potential diagnostic biomarker and therapeutic target, particularly in uveal melanoma.