Dept of Clinical Laboratory, Wuhan Univ, Renmin Hospital, Wuhan 430060, Hubei Province, PR China.
Dept of Clinical Laboratory, Wuhan Univ, Renmin Hospital, Wuhan 430060, Hubei Province, PR China.
Biomed Pharmacother. 2020 Jan;121:109574. doi: 10.1016/j.biopha.2019.109574. Epub 2019 Nov 19.
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.
本研究旨在探讨生长分化因子 15（GDF15）水平，一种应激诱导因子，以及乙型肝炎病毒（HBV）相关肝细胞癌（HCC）男性患者的性激素之间的关系。在这项研究中，我们招募了 298 名男性参与者，包括 83 名健康个体作为对照，67 名慢性乙型肝炎（CHB）患者，56 名 HBV 相关肝硬化（HBV 相关 LC）患者和 92 名 HBV 相关 HCC 患者。测量了血清 GDF15、总睾酮（TT）、雌二醇（E2）、游离睾酮（FT）和其他生化变量。与健康对照组和 CHB 患者相比，HCC 患者的血清 GDF15 水平显著升高，而血清 FT 和游离睾酮/雌二醇比值（FT/E2 比值）显著降低，尽管 HCC 患者与 LC 患者之间无显著差异。此外，巴塞罗那临床肝癌分期 C（BCLC-C）和 BCLC-B 患者的 GDF15 水平高于对照组和 BCLC-A 患者（均 P＜0.05）。此外，与对照组相比，BCLC-B 和 BCLC-C 患者的 FT 水平显著降低（均 P＜0.05）。所有 HCC 分期患者的 FT/E2 比值均显著低于对照组（均 P＜0.05）。相关性分析表明，GDF15 水平与 TT 水平（r =-0.326，P = 0.002）、FT 水平（r =-0.344，P＜0.001）和 E2（r =-0.206，P＜0.05）呈负相关。综上所述，GDF15 的上调、FT 和 FT/E2 比值的下调可能与 HBV 感染的结果和 HCC 的严重程度有关。HBV 相关 HCC 男性患者血清 GDF15 水平升高与性激素呈负相关，提示 GDF15 在低性激素水平和失衡状态下发挥重要作用。因此，通过平衡性激素来调节 GDF15 水平有可能指导新的癌症治疗策略。
