Further Study of Circulating Antibodies to P16, CD25 and FOXP3 in Hepatocellular Carcinoma

PURPOSE: It has been reported that circulating levels of IgG antibodies against p16, CD25 and FOXP3 proteins were significantly changed in patients with lung cancer, breast cancer and esophageal cancer. However, different peptide fragments appear to trigger different immune responses. This work aimed to analyze the alteration of plasma IgG for p16-derived peptide antigen called p16a, CD25-derived peptide antigen called CD25a and a FOXP3-derived antigen in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: An enzyme-linked immunosorbent assay (ELISA) was developed in-house to detect plasma IgG to p16a, CD25a and FOXP3 in 119 patients with HCC and 132 control subjects. RESULTS: Circulating levels of IgG antibodies for all three peptide antigens were significantly higher in HCC patients than control subjects (P<0.001 for all 3 assays); male patients mainly contributed to increase (P<0.01 for all 3 assays). Further analysis showed that plasma anti-p16a, anti-CD25a and anti-FOXP3 IgG levels were increased mainly in patients with intermediate and late-stage HCC (P<0.01 for both assays). Receiver operating characteristic (ROC) curve analysis showed that with a specificity of >95%, the area under the ROC curve (AUC) was 0.62 with 11.4% sensitivity for anti-p16a assay, 0.68 with 14.3% sensitivity for anti-CD25a IgG assay and 0.64 with 10.1% sensitivity for anti-FOXP3 assay. Of the three groups of HCC patients, group 3 (BCLC stage C+D) showed the best sensitivity for the detection of plasma anti-p16a and anti-FOXP3 IgG levels with an AUC of 0.66 and 0.65. CONCLUSION: Circulating IgG antibody to p16a, CD25a and FOXP3 proteins may be a useful biomarker for assessment of HCC prognosis of this malignancy, especially in male patients with HCC.