title: Decrease of Bcl-xL/Bcl-2-associated death promoter in hepatocellular carcinoma indicates poor prognosis.
abstract: Bcl-xL/Bcl-2-associated death promoter (Bad) is a proapoptotic member of Bcl-2 family and plays a key role in tumor development. To explore the expression of Bad and its clinical significance in hepatocellular carcinoma (HCC), we analyzed a large cohort of 437 HCC samples by tissue microarray (TMA)-based immunohistochemistry. Our data showed that Bad expression was markedly decreased in 50.6% (221/437) of HCC tissues, compared with the adjacent nontumorous tissues. Bad expression was closely associated with adverse clinical characters such as clinical stage (P=0.007), tumor size (P=0.008), vascular invasion (P=0.024), tumor differentiation (P=0.018) and AFP level (P=0.039). Furthermore, Kaplan-Meier analysis indicated that low Bad expression was significantly correlated to overall survival (P<0.0001) but not disease-free survival (P=0.587) and recurrence-free survival (P=0.707) of patients with HCC. Stratified survival analysis further confirmed the prognostic value of Bad. Moreover, multivariate analyses revealed that Bad was an independent indicator of overall survival in HCC (hazard ration=0.589, 95% confidence interval: 0.483-0.717, P<0.0001). Collectively, our data suggest that Bad is down-regulated in HCC and serves as a promising biomarker for poor prognosis of patients with this fatal disease.
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine Guangzhou 510060, Guangdong, China ; Department of Pathology, Sun Yat-Sen University Cancer Center Guangzhou 510060, Guangdong, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hu
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine Guangzhou 510060, Guangdong, China ; Department of Pathology, Sun Yat-Sen University Cancer Center Guangzhou 510060, Guangdong, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Fu
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine Guangzhou 510060, Guangdong, China ; Department of Pathology, Sun Yat-Sen University Cancer Center Guangzhou 510060, Guangdong, China.
authors.forename: Shi-Xun
authors.initials: SX
authors.lastname: Lu
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine Guangzhou 510060, Guangdong, China ; Department of Pathology, Sun Yat-Sen University Cancer Center Guangzhou 510060, Guangdong, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Liu
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine Guangzhou 510060, Guangdong, China ; Department of Pathology, Sun Yat-Sen University Cancer Center Guangzhou 510060, Guangdong, China.
authors.forename: Rong-Zhen
authors.initials: RZ
authors.lastname: Luo
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine Guangzhou 510060, Guangdong, China ; Department of Pathology, Sun Yat-Sen University Cancer Center Guangzhou 510060, Guangdong, China.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yun
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine Guangzhou 510060, Guangdong, China ; Department of Pathology, Sun Yat-Sen University Cancer Center Guangzhou 510060, Guangdong, China.
authors.forename: Chris Zhiyi
authors.initials: CZ
authors.lastname: Zhang
keywords: BCL-2; Bad; hepatocellular carcinoma; poor prognosis