Genomic feature and potential therapeutic target for cholangiocarcinoma

Abstract

Abstract Background: The genomic feature of biliary tract carcinoma (BTC) has been characterized, but limited studies focus on the potential therapeutic target for cholangiocarcinoma patients. Methods: 43 BTC patients were enrolled in this retrospective study. Genomic characteristics including genomic alterations and mutational signatures were detected and analyzed. Then, the correlation between the genomic characteristics and clinicopathologic features was investigated. Next, the prognostic significance of these altered genes was evaluated. Besides, personalized targeted therapies for patients harboring potentially actionable targets (PATs) were investigated. Results: Among 43 patients, the genomic mutation was detected in 38 patients. Among these mutations, KRAS (44.2%), TP53(37.2%), ARID1A (18.6%), SMAD4(18.6%), BRCA2, CDKN2A (11.6%), and VEGFA (11.6%) are the most frequently altered cancer-related genes. Besides, germline mutations mainly occurred in ERBB, PI3K/AKT, MAPK, and RAS signaling. Among detected mutations, we found that TP53, STK11, MYC, and ERBB3 are gene alternations with significant prognostic values. In terms of potentially actionable target (PAT) analysis, 19 genes were proposed to be PATs in BTCs. and we found out that 79.1% of patients have Tier II somatic mutation in our cohort. Conclusions: The molecular feature is closely related to clinical characteristics in cholangiocarcinoma patients. In this study, we identified several commonly altered genes in cholangiocarcinoma patients and determined potential prognostic biomarkers and therapeutic targets for cholangiocarcinoma patients.