TP53 Mutation in Circulating exoDNA Correlates with Outcomes of Patients with Hepatocellular Carcinoma.

Abstract

Background: Detection of tumor-specific mutations in exosomal DNA (exoDNA), a promising liquid biopsy material, has been used to assess the prognosis of hepatocellular carcinoma (HCC) patients. This study was the first to use a droplet digital PCR (ddPCR) platform to detect tumor-specific mutations in circulating exoDNA and to evaluate the prognosis of HCC patients.Methods: Blood samples from 40 HCC patients were obtained between 2018 and 2019, with clinically annotated follow-up until 2020. A ddPCR platform was used to detect an HCC tumor-specific mutation in the TP53 gene. We analyzed the correlation between TP53 mutation detected in circulating exoDNA and patient clinical data. The ratio of mutant droplets/total droplets (MD/TD) was calculated according to ddPCR results.Results: TP53 mutations in circulating exoDNA were detected in 33 of the 40 patients (82.5%). Patients with high MD/TD (>62.5%) were more likely to show microvascular invasion (P=0.028) and high MD/TD predicted a shorter recurrence-free survival time (P<0.001).Conclusions: High MD/TD of TP53 detected in serum was associated with microvascular invasion and might be used to predict the prognosis of HCC patients. The diagnostic performance of detecting exosome-derived tumor DNA will likely improve when more mutations in other tumor-specific genes are combined.