American Association for Cancer Research
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Supplementary Table S2 from Combination of an Autoantibody Panel and Alpha-Fetoprotein for Early Detection of Hepatitis B Virus-Associated Hepatocellular Carcinoma

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posted on 2024-05-02, 07:45 authored by Yajing Shen, Jiajun Chen, Jinyu Wu, Tiandong Li, Chuncheng Yi, Keyan Wang, Peng Wang, Changqing Sun, Hua Ye

Supplementary Table S2: RNA sequencing data (GSE22058, GSE121248, and GSE55092) from the Gene Expression Omnibus (GEO) database were downloaded for analyses. These three datasets derived from two microarray platforms (Rosetta/Merck Human RSTA Custom Affymetrix 1.0 microarray and Affymetrix Human Genome U133 Plus 2.0 Array). The GEO query software package was used to download datasets and to collect clinical information. The sample sizes for these three datasets are shown in Supplementary Table S2.


Key Scientific Research Project of Colleges and Universities in Henan Province

Zhengzhou Municipal Science and Technology Bureau (Zhengzhou Science and Technology Bureau)

Henan Provincial Science and Technology Research Project (河南省科技攻关项目)



The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. This study was divided into four phases: discovery, verification, validation, and modeling. A total of four candidate tumor-associated autoantibodies (TAAb; anti-ZIC2, anti-PCNA, anti-CDC37L1, and anti-DUSP6) were identified by human proteome microarray (52 samples) and bioinformatics analysis. Subsequently, these candidate TAAbs were further confirmed by indirect ELISA with two testing cohorts (120 samples for verification and 663 samples for validation). The AUC for these four TAAbs to identify patients with HBV-HCC from chronic hepatitis B (CHB) patients ranged from 0.693 to 0.739. Finally, a diagnostic panel with three TAAbs (anti-ZIC2, anti-CDC37L1, and anti-DUSP6) was developed. This panel showed superior diagnostic efficiency in identifying early HBV-HCC compared with alpha-fetoprotein (AFP), with an AUC of 0.834 [95% confidence interval (CI), 0.772–0.897] for this panel and 0.727 (95% CI, 0.642–0.812) for AFP (P = 0.0359). In addition, the AUC for this panel to identify AFP-negative patients with HBV-HCC was 0.796 (95% CI, 0.734–0.858), with a sensitivity of 52.4% and a specificity of 89.0%. Importantly, the panel in combination with AFP significantly increased the positive rate for early HBV-HCC to 84.1% (P = 0.005) and for late HBV-HCC to 96.3% (P < 0.001). Our findings suggest that AFP and the autoantibody panel may be independent but complementary serologic biomarkers for HBV-HCC detection. We developed a robust diagnostic panel for identifying patients with HBV-HCC from patients with CHB. This autoantibody panel provided superior diagnostic performance for HBV-HCC at an early stage and/or with negative AFP results. Our findings suggest that AFP and the autoantibody panel may be independent but complementary biomarkers for HBV-HCC detection.

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