A novel immunodiagnosis panel for hepatocellular carcinoma based on bioinformatics and the autoantibody‐antigen system

Abstract

Hepatocellular carcinoma (HCC) is a malignancy with a dismal survival rate. The novel autoantibodies panel may provide new insights for the diagnosis of HCC. Biomarkers screened by two methods (bioinformatics and the antigen‐antibody system) were taken as candidate tumor‐associated antigens (TAAs). Enzyme‐linked immunosorbent assay was used to detect the corresponding autoantibodies in 888 samples of verification and validation cohorts. The verification cohort was used to verify the autoantibodies. Samples in the validation cohort were randomly divided into a train set and a test set with the ratio of 6:4. A diagnostic model was established by support vector machines within the train set. The test set further verified the model. Eleven TAAs were selected (AAGAB, C17orf75, CDC37L1, DUSP6, EID3, PDIA2, RGS20, PCNA, TAF7L, TBC1D13, and ZIC2). The titer of six autoantibodies (PCNA, AAGAB, CDC37L1, TAF7L, DUSP6, and ZIC2) had a significant difference in any of the pairwise comparisons among the HCC, liver cirrhosis, and normal control groups. The titer of these autoantibodies had an increasing tendency. Finally, an optimum diagnostic model was constructed with the six autoantibodies. The AUCs were 0.826 in the train set and 0.773 in the test set. The area under the curve (AUC) of this panel for diagnosing early HCC was 0.889. The diagnostic ability of the panel reduced with the progress of HCC. The positive rate of the panel in diagnosing alpha‐fetoprotein (AFP)‐negative patients was 75.6%. For early HCC, the sensitivity of the combination of AFP with the panel was 90.9% and superior to 53.2% of AFP alone. The novel immunodiagnosis panel combining AFP may be a new approach for the diagnosis of HCC, especially for early‐HCC cases.

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

“…Studies have suggested that the combination of multiple anti-TAA autoantibodies as a panel could enhance the detection of cancer [ 20 , 44 , 45 ]. This study combined three anti-TAA autoantibodies as a panel; the panel could identify 68.0% HCC from NC with an accuracy of 88.2%, which was higher than those in any single one of the three autoantibodies.…”

Regulator of G Protein Signaling 20 Correlates with Long Intergenic Non-Coding RNA (lincRNAs) Harboring Oncogenic Potential and Is Markedly Upregulated in Hepatocellular Carcinoma

“…Furthermore, a cumulative effect of (epi-) genomics and oncogenic networks/mechanisms might be contributing to this. Recently, a novel immunodiagnostic assay was developed to screen tumor-associated antigens (TAAs) associated with HCC, that includes RGS20 in a panel of eleven TAAs (AAGAB, C17orf75, CDC37L1, DUSP6, EID3, PDIA2, RGS20, PCNA, TAF7L, TBC1D13, and ZIC2) [ 38 ]. Thus, providing further evidence to support our study indicating the distinctive involvement of RGS20 in HCC.…”

Genetic variants associated with circulating liver injury markers in Mexican Americans, a population at risk for non-alcoholic fatty liver disease

“…DNAJC13 plays a role in vesicle formation and trafficking. Associations between increased levels of DUSP6 and HCC or liver cirrhosis have been reported ( Wu et al, 2022 ). S1PR2 inhibition mitigated liver fibrosis development and S1PR2 blockage has been shown to accelerate HCC progression in mice ( Yoshida et al, 2020 ; Kawai et al, 2021 ).…”