Mica plays an opposite role in hepatocarcinogenesis between hepatitis B and hepatitis C

Abstract

Background and Aims: Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a major risk factor for developing hepatocellular carcinoma (HCC). We recently reported that a SNP rs2596542 located in the MHC class I polypeptide-related chain A (MICA) promoter region was significantly associated with the risk for HCV-induced HCC (C-HCC) and also with serum levels of soluble MICA (sMICA) by genome-wide association study. MICA plays an important role in innate tumor surveillance. In this study, we focused on the possible involvement of MICA in HBV-induced HCC (B-HCC). Methods: The MICA SNP rs2596542 was analyzed in 407 B-HCC cases and 5,657 controls, and in 1,394 C-HCC cases and 5,486 controls. Results: The genetic association analysis revealed a significant association with an SNP rs2596542 (G/A); a G allele increased the risk of B-HCC (P = 0.029 with odds ratio of 1.19), on the other hand, an A allele increased the risk of C-HCC (P = 4.2x10-13 with odds ratio of 1.39).We also found a significant elevation of sMICA in both B-HCC and C-HCC. Moreover, a G allele of SNP rs2596542 was significantly associated with increased sMICA levels in both B-HCC (P = 0.009) and C-HCC (P = 1.4x10-13). Interestingly, B-HCC patients with the high serum level of sMICA (>5 pg/ml) exhibited poorer prognosis than those with the low serum level of sMICA (<5 pg/ml) (P = 0.008). Conclusions: Although MICA increases on cells under stresses including infection and malignant transformation and could be targeted by NK cells, sMICA could block NK cells. Our results indicated the opposite role of MICA variant and sMICA between B-HCC and C-HCC, and thus MICA could be an attractive therapeutic target for both B-HCC and C-HCC.