Cui Yunlong, Li Hua, Zhan Hongjie, Han Tao, Dong Yixuan, Tian Caijuan, Guo Yixian, Yan Fang, Dai Dong, Liu Pengfei
Department of Hepatobiliary Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Department of Endoscopy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Front Oncol. 2021 Sep 17;11:733478. doi: 10.3389/fonc.2021.733478. eCollection 2021.
Liver cancer is a common malignant tumor worldwide, which is a serious threat to the health of people. We try to investigate some mutations and clinical indicators as candidate markers for the development of liver cancer through targeted region capture technology combined with next-generation sequencing. We collected peripheral blood and liver cancer tissue samples from 32 liver patients concurrently. The SeqCap EZ Prime Choice Probe was used to perform the targeted enrichment; this probe captures 1,000 known cancer-associated genes. We calculated the tumor mutation burden (TMB) for each patient. The high-frequency mutations and these relative genes were identified. Eventually, survival analysis was performed based on the mutations and clinical indicators. In 32 liver patients, a total of 29 high-frequency mutations were investigated. They were located in 25 genes, which were enriched in 9 cellular components (CCs), 6 molecular functions (MFs), and 21 biological processes (BPs). Among them, EZH2 c.1544A>G and CCND1 c.839A>T had the highest mutation frequency (5/32). In the protein-protein interaction (PPI) network, EZH2-DNMT3A, NOTCH1-CCND1, and ABL1-CCND1 were the top three pairs. The survival analysis showed that there were significant differences in progression-free survival (PFS) and overall survival (OS) between the Karnofsky performance score (KPS) groups. The PFS and OS in the TMB high group were higher than those in the TMB low group. OS and tumor stage had a remarkable relationship. In conclusion, EZH2 c.1544A>G and CCND1 c.839A>T might be potential biomarkers of liver cancer. TMB might be used as a prognosis and survival indicator of liver cancer.
肝癌是全球常见的恶性肿瘤,严重威胁人类健康。我们试图通过靶向区域捕获技术结合新一代测序来研究一些突变和临床指标,作为肝癌发生发展的候选标志物。我们同时收集了32例肝癌患者的外周血和肝癌组织样本。使用SeqCap EZ Prime Choice探针进行靶向富集;该探针可捕获1000个已知的癌症相关基因。我们计算了每位患者的肿瘤突变负荷(TMB)。鉴定出高频突变及其相关基因。最终,基于这些突变和临床指标进行生存分析。在32例肝癌患者中,共研究了29个高频突变。它们位于25个基因中,富集于9个细胞成分(CCs)、6个分子功能(MFs)和21个生物学过程(BPs)。其中,EZH2 c.1544A>G和CCND1 c.839A>T的突变频率最高(5/32)。在蛋白质-蛋白质相互作用(PPI)网络中,EZH2-DNMT3A、NOTCH1-CCND1和ABL1-CCND1是前三对。生存分析表明,卡诺夫斯基性能评分(KPS)组之间的无进展生存期(PFS)和总生存期(OS)存在显著差异。TMB高分组的PFS和OS高于TMB低分组。OS与肿瘤分期有显著关系。总之,EZH2 c.1544A>G和CCND1 c.839A>T可能是肝癌的潜在生物标志物。TMB可能用作肝癌的预后和生存指标。