Abstract
INTRODUCTION: Treatment options for biliary tract cancer (BTC) are very limited. It is necessary to investigate actionable genes and candidate drugs using a sophisticated knowledgebase (KB) and characterize BTCs immunologically for evaluating the actionability of molecular and immune therapies. MATERIALS AND METHODS: The genomic and transcriptome data of 219 patients with BTC who underwent surgery were analyzed. Actionable mutations and candidate drugs were annotated using the largest available KB of the Asian population (CancerSCAN(®)). Predictive biomarkers of immune checkpoint inhibitors were analyzed using DNA and RNA sequencing data. RESULTS: Twenty-two actionable genes and 43 candidate drugs were annotated in 74 patients (33.8%). The most frequent actionable genes were PTEN (7.3%), CDKN2A (6.8%), KRAS (6.4%). BRCA2, CDKN2A, and FGFR2 mutations were most frequently identified in case of intrahepatic cholangiocarcinoma. PTEN and CDKN2A mutations were associated with significantly shorter overall survival. PD-L1 and PD-1 expression was significantly higher in case of extrahepatic cholangiocarcinoma and T-cell-high expression. In total, 49.7% of cases were evaluated as having actionability for molecular therapy or immune checkpoint inhibitors. CONCLUSIONS: Identifying actionable genes and candidate drugs using the KB contribute to the development of therapeutic drugs and personalized treatment for BTC.