Cancer medicine · 2023
Immune checkpoint inhibitor-related molecular markers predict prognosis in extrahepatic cholangiocarcinoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Jin Bao, Wang Yuxin, Zhang Baoluhe, Xu Haifeng, Lu Xin, Sang Xinting, Wang Wenze, Mao Yilei, Chen Pengxiao, Wang Shun, Qian Zhirong, Wang Yingyi, Du Shunda
Аннотация
BACKGROUND: Therapeutic approaches for extrahepatic cholangiocarcinoma (EHCC) are limited, due to insufficient understanding to biomarkers related to prognosis and drug response. Here, we comprehensively assess the molecular characterization of EHCC with clinical implications.
METHODS: Whole-exome sequencing (WES) on 37 tissue samples of EHCC were performed to evaluate genomic alterations, tumor mutational burden (TMB) and microsatellite instability (MSI).
RESULTS: Mutation of KRAS (16%) was significantly correlated to poor OS. ERBB2 mutation was associated with improved OS. ERBB2, KRAS, and ARID1A were three potentially actionable targets. TMB ≥10 mutations per megabase was detected in 13 (35.1%) cases. Six patients (16.2%) with MSIsensor scores ≥10 were found. In multivariate Cox analysis, patients with MSIsensor sore exceed a certain threshold (MSIsensor score ≥0.36, value approximately above the 20th percentile as thresholds) showed a significant association with the improved OS (HR = 0.16; 95% CI: 0.056-0.46, p < 0.001), as well as patients with both TMB ≥3.47 mutations per megabase (value approximately above the 20th percentile) and MSIsensor score ≥0.36.
CONCLUSIONS: TMB and MSI are potential biomarkers associated with better prognosis for EHCC patients. Furthermore, our study highlights important genetic alteration and potential therapeutic targets in EHCC.
METHODS: Whole-exome sequencing (WES) on 37 tissue samples of EHCC were performed to evaluate genomic alterations, tumor mutational burden (TMB) and microsatellite instability (MSI).
RESULTS: Mutation of KRAS (16%) was significantly correlated to poor OS. ERBB2 mutation was associated with improved OS. ERBB2, KRAS, and ARID1A were three potentially actionable targets. TMB ≥10 mutations per megabase was detected in 13 (35.1%) cases. Six patients (16.2%) with MSIsensor scores ≥10 were found. In multivariate Cox analysis, patients with MSIsensor sore exceed a certain threshold (MSIsensor score ≥0.36, value approximately above the 20th percentile as thresholds) showed a significant association with the improved OS (HR = 0.16; 95% CI: 0.056-0.46, p < 0.001), as well as patients with both TMB ≥3.47 mutations per megabase (value approximately above the 20th percentile) and MSIsensor score ≥0.36.
CONCLUSIONS: TMB and MSI are potential biomarkers associated with better prognosis for EHCC patients. Furthermore, our study highlights important genetic alteration and potential therapeutic targets in EHCC.