17β-HSD13 has sex-based differential expression in Hepatitis C virus-induced cirrhosis and hepatocellular carcinoma

Abstract

Background: Sex-based differences are observed in chronic hepatitis C virus (HCV) infections leading to cirrhosis and hepatocellular carcinoma (HCC). We previously showed that liver estrogen receptor (ER-) mediated sex-based differences exist in cirrhosis and HCC. Liver ER-binding may lead to protective effects in pre-menopausal women. This study aimed to determine sex-based differential role of 17βHSD13 in development of cirrhosis and HCC. We hypothesized that chronic HCV infection leads to dysregulated 17β-HSD13 in male cirrhosis and progression to HCC.

Methods: 65 (normal, cirrhosis, HCC) liver tissues were obtained from NIH Liver Tissue Bank. DIA proteomics mapped 4445 proteins, including 17β-HSD13. Clinical correlation with bilirubin, AST, ALP, and creatinine was determined (spearman’s). Immunohistochemistry validated 17β-HSD13 protein expression in tissues.

Results: 17β-HSD13 had significantly lower expression in male cirrhosis group than females (P<0.05). In contrast, 17β-HSD13 expression in normal males was significantly greater than normal females (P<0.05). In HCC group, the expression in males was down-regulated compared to HCC females (P<0.05). Bilirubin values showed negative correlation with 17β-HSD13 expression (P<0.05) between cirrhosis and HCC (males alone and combined sex data).

Conclusions: Low 17β-HSD13 levels may predict worse disease in males with cirrhosis or HCC serving as disease biomarker. This novel report shows sex-based differences in 17β-HSD13 during HCV-induced cirrhosis development.