Identification of NOTCH2 as a prognostic marker for cholangiocarcinoma

Cholangiocarcinoma (CCA) is a rare malignancy originating from the hepatobiliary epithelium, accounting for 3–5% of all gastrointestinal cancers worldwide. CCA is notoriously difficult to diagnose and is associated with a high mortality rate. While most cases lack identifiable predisposing factors, emerging evidence suggests that molecular therapies targeting fibroblast growth factor receptor and isocitrate dehydrogenase show promise for specific CCA patients. This study employed a series of comprehensive bioinformatics analyses, survival analyses, immunohistochemistry, and drug sensitivity screening. We decoded the dynamic changes in cell populations between cholangiocarcinoma and paired healthy tissues, revealing that JAG1-NOTCH signaling significantly contributes to CCA pathogenesis. Higher NOTCH2 expression was correlated with poor prognosis and validated as a proliferative promoter in cell lines. Additionally, we identified four potential drugs targeting NOTCH2. These findings provide new insights into the molecular basis of NOTCH2-mediated promotion of tumor activity and suggest NOTCH2 as a potential therapeutic target for CCA treatment.