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Int. J. Mol. Sci. 2015, 16(9), 22662-22675; doi:10.3390/ijms160922662

SOCS3 Methylation Predicts a Poor Prognosis in HBV Infection-Related Hepatocellular Carcinoma

1
Department of Radiotherapy, Harbin Medical University Cancer Hospital, Harbin 150081, China
2
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: William Cho
Received: 18 August 2015 / Revised: 11 September 2015 / Accepted: 11 September 2015 / Published: 18 September 2015
(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)
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Abstract

Suppressor of cytokine signaling 3 (SOCS3) plays crucial roles in JAK/STAT signaling pathway inhibition in hepatocellular carcinoma (HCC). However, the methylation status of SOCS3 in HBV infection-related HCC and the relationship between SOCS3 methylation and the clinical outcome remain unknown. Here, we reported that in HCC tumor tissues, two regions of the CpG island (CGI) in the SOCS3 promoter were subjected to methylation analysis and only the region close to the translational start site of SOCS3 was hypermethylated. In HCC tumor tissues, SOCS3 showed an increased methylation frequency and intensity compared with that in the adjacent non-tumor tissues. Moreover, SOCS3 expression was significantly down-regulated in HCC cell lines and tumor tissues, and this was inversely correlated with methylation. Kaplan–Meier curve analysis revealed that in patients with an hepatitis B virus (HBV) infection background, SOCS3 hypermethylation was significantly correlated with a poor clinical outcome of HCC patients. Our findings indicated that SOCS3 hypermethylation has already happened in non-tumor tissues and increased in both frequency and intensity in tumor tissues. This suggests that the methylation of SOCS3 could predict a poor prognosis in HBV infection-related HCC patients. View Full-Text
Keywords: hepatitis B virus; hepatitis C virus hepatocellular carcinoma; methylation; prognosis; SOCS3; translational start site hepatitis B virus; hepatitis C virus hepatocellular carcinoma; methylation; prognosis; SOCS3; translational start site
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zhang, X.; You, Q.; Zhang, X.; Chen, X. SOCS3 Methylation Predicts a Poor Prognosis in HBV Infection-Related Hepatocellular Carcinoma. Int. J. Mol. Sci. 2015, 16, 22662-22675.

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