Bcl-2 expression is a poor predictor for hepatocellular carcinoma prognosis of andropause-age patients

Xiao-Fei Zhang, Xin Yang, Hu-Liang Jia, Wen-Wei Zhu, Lu Lu, Wei Shi, Hao Zhang, Jin-Hong Chen, Yi-Feng Tao, Zheng-Xin Wang, Jun Yang, Lian-Xin Wang, Ming Lu, Yan Zheng, Jing Zhao, Qiong-Zhu Dong, Lun-Xiu Qin

Abstract


Objective: The expression of B-cell lymphoma 2 (Bcl-2) seems to be influenced by the endocrine environment. Numerous reportsdemonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With the exception of estrogen-relatedtumors, androgen-related tumors have shown their characteristics in Bcl-2 expression. In this study, the status of Bcl-2 expressionin male hepatocellular carcinoma (HCC) patients was examined to verify the high incidence of HCC in males.

Methods: Tumor tissue microarray was used to examine Bcl-2 expression levels in 374 HCC cases including 306 males and 68females. Kaplan-Meier method, log-rank test, and Cox proportional hazards model were applied to investigate the predictive valueof Bcl-2 in HCC patients.

Results: Immunohistochemistry analysis showed that male patients with higher Bcl-2 levels had significantly longer mediansurvival time and recurrence time than those with lower levels. However, no significant differences in outcomes were foundbetween different Bcl-2 levels in female patients. When the male patients were stratified into several age points, the level of Bcl-2expression showed poorer predictive efficiency in the 45–49 and 55–60 age groups in andropause-age patients compared withother age groups. Bcl-2 was an independent prognostic factor for both overall survival (P < 0.0001) and recurrence time (P =0.0001) in male patients. After excluding male patients in the 45–60 age group, the predictive efficiency was enhanced (n = 147,OS, P = 0.0002, TTR, P < 0.0001).

Conclusions: Bcl-2 expression is an independent predictor of survival and recurrence in male HCC. Bcl-2 levels may also beregulated by androgens or androgen receptors in male HCC patients. Bcl-2 levels change and exhibit poor predictive efficiencywhen androgen levels vary dramatically (andropause age).


Keywords


Hepatocellular carcinoma; andropause; Bcl-2; prognosis; androgen

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