Abstract:

Objective To discuss the expression characteristics of natural autoantibodies against the apoptosis inhibitor gene BIRC5 in plasma of the patients with hepatocellular carcinoma （HCC） and their clinical significances， and to evaluate the potential value as the prognostic biomarker for HCC. Methods A total of 119 HCC patients were enrolled as case group. According to the Barcelona Clinic Liver Cancer （BCLC） staging system， the patients were divided into stages 0+A stage， B stage， and C+D stage. A total of 132 healthy control subjects （healthy control group） were recruited from the physical examination center of our hospital. The blood samples were collected from all the subjects. Two highly efficient linear antigenic peptides （BIRC5a and BIRC5b） for detection were designed and synthesized using epitope prediction software； optimized enzyme-linked immunosorbent assay （ELISA） method was used to detect the levels of BIRC5 natural autoantibodies in plasma of the subjects in two groups； receiver operating characteristic （ROC） curve was plotted to evaluate diagnostic performance； Pearson/Spearman correlation analysis was used to examine the association between antibody levels and clinical indicators ［alpha-fetoprotein （AFP）， liver function， carcinoembryonic antigen （CEA）， carbohydrate antigen 199 （CA199）， total bilirubin （TBil）， albumin （Alb）， and prothrombin time （PT）］. Results Compared with healthy control group， the levels of BIRC5a and BIRC5b natural autoantibodies in plasma of male HCC patients in case group were increased （P<0.05）， while no statistically significant difference was observed in female HCC patients （P>0.05）. Compared with healthy control group， the level of BIRC5a natural autoantibodies in plasma of the patients with BCLC stage C+D in case group was increased （P<0.05）. The correlation analysis results showed that the level of BIRC5a natural autoantibodies increased with higher BCLC stage （r=0.132， P<0.05）， was positively correlated with increased alkaline phosphatase （ALP） and prolonged PT （r=0.328， P<0.05； r=0.247， P<0.05）， and was negatively correlated with decreased Alb （r=-0.423， P<0.01）. The ROC curve analysis results showed that the area under the curve （AUC） for BIRC5a was 0.559； the AUC for BIRC5b was 0.543； the combined analysis AUC was 0.561， and it demonstrated the best diagnostic performance （AUC=0.569） under the optimal diagnostic cut-off value， with a sensitivity of 45.1% and a specificity of 74.6% for diagnosing HCC. Conclusion BIRC5a natural autoantibody is a potential biomarker for HCC prognosis， particularly in male HCC patients. Its elevated plasma level is significantly associated with disease progression and deterioration of liver function， suggesting it may serve as an independent risk factor affecting the prognosis of HCC.

Key words: Apoptosis inhibitor proteins, Natural autoantibodies, Hepatocellular carcinoma, Prognostic biomarkers