Objective To explore the role of combined detection of cell free BMPR1A and PLAC8gene methylation in plasma in predicting postoperative recurrence of hepatocellular carcinoma.Methods Case series study.Patients with stage Ⅰ-Ⅳ hepatocellular carcinoma who were treated at the Third Affiliated Hospital of Sun-Yat-sen University from January 2022 to July 2023 were selected.All enrolled patients underwent alpha fetoprotein(AFP)and imaging assessments 1 month,3 months,6 months,9 months,and 12 months after treatment.Simultaneously,peripheral blood of patients was extracted for plasma circulating tumor DNA(ctDNA)methylation detection,and the results of free BMPR1A and PLAC8 gene methylation detection in patients'plasma after treatment were compared with the positive rate of traditional tumor marker AFP detection.Draw the receiver operating characteristic curve(ROC)of the subjects to demonstrate the effectiveness of this method in predicting the recurrence of hepatocellular carcinoma.Based on the results of cell free DNA methylation and whether AFP is more than 7 μg/L,hepatocellular carcinoma patients were divided into high-risk methylation group(12 cases),low-risk methylation group(21 cases),high-risk AFP group(15 cases),and Kaplan Meier survival analysis was performed on them.Results The sensitivity and specificity of combined detection of free BMPR1A PLAC8 gene methylation in plasma for predicting liver cancer recurrence were 66.7%and 88.9%,respectively.The area under curve(AUC)of BMPR1A PLAC8 gene methylation detection for liver cancer recurrence were 0.770 and 0.778,and the AFP was 0.522 in ROC curve analysis.Compared to imaging examinations,cell free DNA methylation detection can detect the recurrence of hepatocellular carcinoma on average by 58.3 days in advance(53.8 days vs 112.1 days).The progression free survival rate of the high-risk group based on free DNA methylation prediction at 400 days was 22.2%,significantly lower than the low-risk group(76.2%,P<0.001).Conclusion Compared to AFP,detecting the methylation of BMPR1A and PLAC8 genes can predict the recurrence of hepatocellular carcinoma more accurately,making it a practical method for monitoring liver cancer recurrence.
关键词
DNA甲基化/循环肿瘤DNA/肝肿瘤/复发
Key words
DNA methylation/Circulating tumor DNA/Liver neoplasms/Recurrence