肝硬化相關細胞激素對B型肝炎誘導肝細胞癌之預測：蛋白質微陣列分析

Abstract

Background Early identification of high risk population for liver cirrhosis may be beneficial to hepatitis B virus (HBV) carriers and their prognosis on hepatocellular carcinoma (HCC). We aimed to identify differently expressed cytokines in plasma between clinical liver cirrhosis patients and asymptomatic HBV carriers as biomarkers for HCC prediction. Methods A total of 174 cytokines were assessed in plasma from 16 HBsAg carriers at different stages of liver cirrhosis using cytokine antibody microarrays. Ten promising cytokines were later evaluated in a case-control study including 49 HCC cases and 50 matched controls nested within a longitudinal cohort study of HBsAg carriers by using quantitative antibody arrays. Blood samples from each study subject were collected up to 16 years before diagnosis of HCC. Results Forty-five cytokines were differentially expressed among asymptomatic carriers, Child-Pugh stage A patients and Child-Pugh stage B/C patients (parametric P-value range: 0.0006-0.0487, empirical P-value range: 0.0003-0.0556, false-discovery rate q-value range=0.0713-0.1244). Evaluation of a subset of 10 cytokines, including ICAM-2, MCP-1, EGF, CXCL-16, IGFBP-2, sTNFRII, TIMP4, Fas, RANTES, and TIMP-1, by a nested case-control study showed that only plasma ICAM-2 levels were significantly different between HCC cases and controls at baseline (P-value for Wilcoxon sum rank test = 0.0413). Plasma ICAM-2 levels exhibited an accuracy (AUC=0.6208) comparable to HBV viral load (AUC=0.6022) and superior to serum ALT (AUC=0.5965) for prediction of HCC. Conclusion Results of this study suggested that ICAM-2 may serve as a promising noninvasive biomarker for prediction of HCC development. Key Words Cytokines, Hepatitis B, liver cirrhosis, hepatocellular carcinoma, microarrays