Correlation Analysis Between Circulating Tumor DNA And Prognosis In Patients With Hepatocellular Carcinoma

Background and objective:Liver cancer is the most one of the highest morbidity and mortality tumor around the world,Hepatocellular carcinoma(HCC)is the major pathological type.As the ever-advancing research in HCC,the molecular targets used in liquid biopsy for HCC was keeping appearing.And circulating tumor DNA(ctDNA)as one kind of these molecular targets has been used in research of different stages of HCC.However,the assay to assess the ctDNA was not the same,in these methods,a bloodbased assay derived from copy number aberrations(CNAs)and the fragment size(FS)of ctDNA was developed.This method was effective in the diagnosis of hepatocellular carcinoma(HCC).However,its application in predicting the prognosis of HCC has not been thoroughly studied.Therefore,our aim was to evaluate the prognostic value of this assay in HCC patients.Method: Ninety-three HCC patients diagnosed with HCC From March 2018 to June 2021 were enrolled,and Clinical and ctDNA date were collected and analyzed retrospectively.Patients were classified according to different ctDNA scores,which included surgery and tumor treatment as factors.Then,using the chi-square test,we compared many critical factors such as the sex,age,serum hepatitis B virus antigen(HBs Ag),Child?Pugh stage,alpha-fetoprotein(AFP),PIVKA-II,the largest tumor size,macrovascular invasion,and TNM stage.Survival analysis of HCC patients with different levels of ctDNA scores was performed using the Kaplan?Meier method.Risk factors were identified using the multivariate Cox proportional hazard analysis.Result: HCC patients with high ctDNA scores tended to have higher AFP(P < 0.001),PIVKA-II(P < 0.001)levels,a larger tumor size(P < 0.001),a higher rate of macrovascular invasion(P = 0.001)and a higher TNM stage(P = 0.001).HCC patients with ctDNA scores > 0.61199 had worse over-survival(OS)outcomes.Univariate analysis indicated that a ctDNA scores > 0.61199,BMI > 21.79,WBC > 6.38 kg/m2,NLR > 2.33,NEU > 3.77 g/L,MOMO > 0.455 g/L,ALT > 34.0 U/L,TBIL > 20.15 μmol/L,DBIL > 3.65 μmol/L,IBIL > 10.65 μmol/L,ALB > 35.6 g/L,GLB > 29.75 g/L,APTT > 37.6 S,Fib > 2.865 g/L,PIVKA-II > 2454 m AU/m L,AFP > 40 ng/m L,a larger tumor size,and a tumor number > 3 were correlated with overall survival(OS).Cox regression analysis suggested that a DNA score > 0.61199,AFP > 40 ng/ml,ALB ≥ 35.6 g/l,and a tumor number were independently correlated with OS.Conclusion: A higher ctDNA score was associated with a poorer prognosis,which may be a potential clinical reference index for predicting the prognosis of patients with HCC.