Circulating levels of growth differentiation factor 15 and sex hormones in male patients with HBV-associated hepatocellular carcinoma.

This study aimed to investigate the levels of growth differentiation factor 15 (GDF15), a stress-induced factor, and sex hormones in male patients with HBV-related hepatocellular carcinoma (HCC) and the association between the two. In this study, we recruited 298 male participants including 83 healthy individuals as controls, 67 patients with chronic hepatitis B (CHB), 56 patients with HBV-related liver cirrhosis (HBV-related LC), and 92 patients with HBV-related HCC. Serum levels of GDF15, total testosterone (TT), estradiol (E2), free testosterone (FT) and other biochemical variables were measured. Serum GDF15 levels were significantly increased and serum FT and free testosterone/estradiol ratio (FT/E2 ratio) were significantly decreased in HCC compared with healthy controls and CHB patients, though there was no significant difference between HCC and LC patients. Furthermore, the Barcelona Clinic Liver Cancer stage C (BCLC-C) and BCLC-B patients had higher GDF15 levels than those in the controls and BCLC-A patients (all P＜0.05). In addition, levels of FT were significantly reduced in BCLC-B and BCLC-C patients compared to controls (all P＜0.05). The FT/E2 ratio was significantly decreased in all HCC staging patients compared with controls (all P＜0.05). Correlation analyses showed that GDF15 levels were inversely correlated with TT levels (r =-0.326, P = 0.002), FT levels (r =-0.344, P＜0.001) and E2 (r =-0.206, P＜0.05). Together, these results suggest that upregulation of GDF15, downregulation of FT and FT/E2 ratio may be involved in the outcome of HBV infection and the severity of HCC. And high levels of serum GDF15 were negatively associated with sex hormones in male patients with HBV-related HCC, suggesting an important role of GDF15 in the presence of low and imbalanced sex hormones levels. Thus, regulation of GDF15 levels by rebalancing sex hormones has the potential to guide strategies for new cancer therapeutics.