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.
Subject(s)
Carcinoma, Hepatocellular , Circulating Tumor DNA , Liver Neoplasms , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/surgery , Circulating Tumor DNA/genetics , Hepatectomy , Humans , Liver Neoplasms/genetics , Liver Neoplasms/surgery , Mutation , Prognosis , Tumor Suppressor Protein p53/geneticsABSTRACT
OBJECTIVE: To understand the dynamics of schistosomiasis situation so as to provide the evidence for formulating the prevention and control scheme in Erlang Village, Yueyang County, Hunan Province. METHODS: The schistosomiasis prevalence and Oncomelania snail status were investigated from 2005 to 2012. RESULTS: The schistosome infection rates of the residents decreased from 2.76% in 2005 to 0.54% in 2012 and the decline rate was 80.43%; the infection rates of the livestock decreased from 8.70% in 2005 to 0 in 2012. No snails were found in the inner embankment over the eight-year period. The density of the infected snails was 0.0005 per 0.1 m(2) in 2005, but no positive snails were found from 2009 to 2012 outside the embankment. CONCLUSION: The schistosome infections of people and livestock and the status of the intermediate host snails have achieved the criteria of schistosomiasis transmission control.