TP53R249S mutation detected in circulating tumour DNA is associated with Prognosis of hepatocellular carcinoma patients with or without hepatectomy
TP53R249S mutation detected in circulating tumour DNA is associated with Prognosis of hepatocellular carcinoma patients with or without hepatectomy
复制标题
循环肿瘤DNA中检测到的TP53R249S突变与接受或不接受肝切除术的肝细胞癌患者的预后相关
DOI：
10.1111/liv.14581
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发表时间：
2020-07-07
影响因子：
6.7
通讯作者：
Jiang，De-Ke
中科院分区：
文献类型：
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作者：
Shen，Ting;Li，Shan-Feng;Jiang，De-Ke
背景与目的TP53的体细胞突变R249S在肝细胞癌中非常常见。方法对895例肝细胞癌患者的3个队列进行分析，采用直接测序的方法检测肝切除患者(队列1，N=3260)组织标本中的TP53基因突变谱。研究R249S和其他常见错义突变的生物学功能及其与肝癌患者总生存期(OS)和无进展生存期(PFS)的关系。通过滴状数字聚合酶链式反应(DdPCR)检测循环肿瘤DNA(CtDNA)中的R249S，并分析其与OS和PR的关系。R249S的过表达导致的恶性表型比其他三个已鉴定的TP53重复错义突变更严重。此外，R249S，而不是其他错义突变，与肝细胞癌患者的OS(P=0.006)和PFS(P=1.01)显著相关。与队列1的结果一致，携带R249S的2和3组肝癌患者的OS(P=8.291×10−7和2.608×10−7)和PFS(2组和3组分别为P=5.115×10−7和5.900×10−13)均低于无R249S突变的患者。
Background and AimsSomatic mutation R249S inTP53is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC.MethodsWe analysed three cohorts including 895 HCC patients.TP53mutation spectrum was examined by direct sequencing of genomic DNA from tissue specimens in HCC patients with hepatectomy (Cohort 1, N = 260). R249S and other recurrent missense mutations were assessed for their biological functions and associations with overall survival (OS) and progression‐free survival (PFS) of HCC patients in Cohort 1. R249S within circulating tumour DNA (ctDNA) was detected through droplet digital polymerase chain reaction (ddPCR) and its association with OS and PRS was analysed in HCC patients with (Cohort 2, N = 275) or without (Cohort 3, N = 360) hepatectomy.ResultsIn Cohort 1, R249S occupied 60.28% of allTP53mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identifiedTP53recurrent missense mutations. Additionally, R249S, but not other missense mutations, was significantly associated with worse OS (P= .006) and PFS (P= .01) of HCC patients. Consistent with the results in Cohort 1, HCC patients in Cohorts 2 and 3 with R249S had worse OS (P= 8.291 × 10−7and 2.608 × 10−7in Cohorts 2 and 3, respectively) and PFS (P= 5.115 × 10−7and 5.900 × 10−13in Cohorts 2 and 3, respectively) compared to those without this mutation.ConclusionsTP53R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy.