Novel genetic alterations in liver cancer distinguish distinct clinical outcomes and combination immunotherapy responses

作者：Yizhou Wang, Peipei Shang, Chang Xu, Wei Dong, Xiaofeng Zhang, Yong Xia, Chengjun Sui, Cheng Yang · 发表于：Frontiers in Pharmacology · 年份：2024 · DOI：10.3389/fphar.2024.1416295 · 被引用次数：4 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Hepatocellular Carcinoma Treatment and Prognosis、RNA modifications and cancer

Introduction: Genomic profiling has revolutionized therapeutic interventions and the clinical management of liver cancer. However, pathogenetic mechanisms, molecular determinants of recurrence, and predictive biomarkers for first-line treatment (anti-PD-(L)1 plus bevacizumab) in liver cancer remain incompletely understood. Materials and methods: Targeted next-generation sequencing (tNGS) (a 603-cancer-gene panel) was applied for the genomic profiling of 232 hepatocellular carcinoma (HCC) and 22 intrahepatic cholangiocarcinoma (ICC) patients, among which 47 unresectable/metastatic HCC patients underwent anti-PD-1 plus bevacizumab therapy. Genomic alterations were estimated for their association with vascular invasion (VI), location of onset, recurrence, overall survival (OS), recurrence-free survival (RFS), and anti-PD-1 plus bevacizumab therapy response. Results: The genomic landscape exhibited that the most commonly altered genes in HCC were TP53 , FAT3 , PDE4DIP , KMT2C , FAT1 , and MYO18A , while TP53 , FAT1 , FAT3 , PDE4DIP , ROS1 , and GALNT11 were frequently altered in ICC; notably, KRAS (18.18% vs. 1.29%) and BAP1 (13.64% vs. 1.29%) alterations were significantly more prevalent in ICC. Comparison analysis demonstrated the distinct clinicopathological/genomic characterizations between Chinese and Western HCC cohorts. Genomic profiling of HCC underlying VI showed that LDLR , MSH2 , KDM5D , PDE3A , and FOXO1 were frequently altered in the VI group compared to patients wit...