Autoantibodies to PAX5, PTCH1, and GNA11 as Serological Biomarkers in the Detection of Hepatocellular Carcinoma in Hispanic Americans

Abstract

Studies have demonstrated that autoantibodies to tumor-associated antigens (TAAs) may be used as efficient biomarkers with low-cost and highly sensitive characteristics. In this study, an enzyme-linked immunosorbent assay (ELISA) was conducted to analyze autoantibodies to paired box protein Pax-5 (PAX5), protein patched homolog 1 (PTCH1), and guanine nucleotide-binding protein subunit alpha-11 (GNA11) in sera from Hispanic Americans including hepatocellular carcinoma (HCC) patients, patients with liver cirrhosis (LC), patients with chronic hepatitis (CH), as well as normal controls. Meanwhile, 33 serial sera from eight HCC patients before and after diagnosis were used to explore the potential of these three autoantibodies as early biomarkers. In addition, an independent non-Hispanic cohort was used to evaluate the specificity of these three autoantibodies. In the Hispanic cohort, at the 95.0% specificity for healthy controls, 52.0%, 44.0%, and 44.0% of HCC patients showed significantly elevated levels of autoantibodies to PAX5, PTCH1, and GNA11, respectively. Among patients with LC, the frequencies for autoantibodies to PAX5, PTCH1, and GNA11 were 32.1%, 35.7%, and 25.0%, respectively. The area under the ROC curves (AUCs) of autoantibodies to PAX5, PTCH1, and GNA11 for identifying HCC from healthy controls were 0.908, 0.924, and 0.913, respectively. When these three autoantibodies were combined as a panel, the sensitivity could be improved to 68%. The prevalence of PAX5, PTCH1, and GNA11 autoantibodies has already occurred in 62.5%, 62.5%, or 75.0% of patients before clinical diagnosis, respectively. In the non-Hispanic cohort, autoantibodies to PTCH1 showed no significant difference; however, autoantibodies to PAX5, PTCH1, and GNA11 showed potential value as biomarkers for early detection of HCC in the Hispanic population and they may monitor the transition of patients with high-risk (LC, CH) to HCC. Using a panel of the three anti-TAA autoantibodies may enhance the detection of HCC.