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TP53 R249S mutation detected in circulating tumour DNA is associated with Prognosis of hepatocellular carcinoma patients with or without hepatectomy
Author(s) -
Shen Ting,
Li ShanFeng,
Wang JiaLin,
Zhang Ting,
Zhang Song,
Chen HaiTao,
Xiao QianYi,
Ren WeiHua,
Liu Chao,
Peng Bo,
Ji XiaoNa,
Yang Yang,
Lu PeiXin,
Chen TaoYang,
Yu Long,
Ji Yuan,
Jiang DeKe
Publication year - 2020
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14581
Subject(s) - hepatocellular carcinoma , missense mutation , cohort , medicine , hepatectomy , oncology , germline mutation , liver cancer , cancer research , gastroenterology , mutation , resection , biology , surgery , gene , genetics
Abstract Background and Aims Somatic mutation R249S in TP53 is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC. Methods We analysed three cohorts including 895 HCC patients. TP53 mutation 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. Results In Cohort 1, R249S occupied 60.28% of all TP53 mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identified TP53 recurrent 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 −7 and 2.608 × 10 −7 in Cohorts 2 and 3, respectively) and PFS ( P = 5.115 × 10 −7 and 5.900 × 10 −13 in Cohorts 2 and 3, respectively) compared to those without this mutation. Conclusions TP53 R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy.