Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis
Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis
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DOI：
10.1016/j.jhep.2021.04.049
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发表时间：
2021-09-15
影响因子：
25.7
通讯作者：
Llovet, Josep M.
中科院分区：
文献类型：
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作者：
Pinyol, Roser;Torrecilla, Sara;Llovet, Josep M.
背景和目标：非酒精性脂肪性肝炎（NASH）相关的肝细胞癌（HCC）在全球范围内不断增加，但其分子特征尚未明确。我们的目的是确定独特的分子特征NASH-HCC相比，其他HCC aetiology.Methods：我们收集了80 NASH-HCC和125 NASH样本从5个机构。将表达阵列（n = 53 NASH-HCC; n = 74 NASH）和全外显子组测序（n = 52 NASH-HCC）数据与其他病因的HCC（n = 184）进行比较。通过RNA-seq/表达阵列分析三种NASH-HCC小鼠模型（n = 20）。激活素A受体2A（ACVR 2A）在肝癌细胞中被沉默，并通过比色法和集落形成测定法评估增殖。结果：NASH-HCC肿瘤的突变谱显示，TERT启动子（56%）、CTNNB 1（28%）、TP 53（18%）和ACVR 2A（10%）是最常见的突变基因。NASH-HCC中ACVR 2A突变率高于其他HCC病因（10% vs. 3%，p
Background and Aims: Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterising NASH-HCC compared to other HCC aetiologies.Methods: We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n = 53 NASH-HCC; n = 74 NASH) and whole exome sequencing (n = 52 NASH-HCC) data were compared to HCCs of other aetiologies (n = 184). Three NASH-HCC mouse models were analysed by RNA-seq/expression-array (n = 20). Activin A receptor type 2A (ACVR2A) was silenced in HCC cells and proliferation assessed by colorimetric and colony formation assays.Results: Mutational profiling of NASH-HCC tumours revealed TERT promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% vs. 3%, p