Low expression of Beclin 1, associated with high Bcl-xL, predicts a malignant phenotype and poor prognosis of gastric cancer

• Published in: Autophagy 2012-03, Vol.8 (3), p.389-400
• Main Authors: Zhou, Wei-Hua, Tang, Fang, Xu, Jie, Wu, Xing, Yang, Shao-Bing, Feng, Zhi-Ying, Ding, Yun-Gang, Wan, Xiang-Bo, Guan, Zhong, Li, Hai-Gang, Lin, Dong-Jun, Shao, Chun-Kui, Liu, Quentin
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; apoptosis; Apoptosis Regulatory Proteins - metabolism; autophagy; bcl-X Protein - metabolism; Bcl-xL; Beclin 1; Binding; Biology; biomarker; Bioscience; Calcium; Cancer; Cell; Cell Line, Tumor; Cycle; Disease-Free Survival; Female; gastric cancer; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Humans; Kaplan-Meier Estimate; Landes; Male; Membrane Proteins - metabolism; Middle Aged; Multivariate Analysis; Organogenesis; Phenotype; Prognosis; Proportional Hazards Models; Proteins; ROC Curve; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology
• ISSN: 1554-8627; 1554-8635
• DOI: 10.4161/auto.18641

Recent studies have suggested that dysregulation of autophagy plays a pivotal role in tumorigenesis. Here, we determined the prognostic value of autophagy-related protein Beclin 1 in gastric cancer. A total of 153 primary gastric cancer patients were subjected to analysis of Beclin 1 expression and survival prognosis. Among them, 68 patients were assigned randomly and used as a training set to generate a cutoff score for Beclin 1 expression by receive operating characteristic (ROC) curve analysis. The ROC-generated cutoff score was subjected to analyze the association of Beclin 1 with clinical characteristics and patient outcome. In a testing set (n = 85) and overall patients (n = 153), both univariate and multivariate analysis found that low expression of Beclin 1 predicted adverse overall survival and progression-free survival for gastric cancer patients. Furthermore, in each stage of gastric cancer patients, Beclin 1 expression was a prognostic indicator in patients with stage II, III and IV. Importantly, a reverse relationship between Beclin 1 and Bcl-xL expression was demonstrated. In patients of elevated Bcl-xL expression, a subset with lower Beclin 1 expression displayed an inferior overall survival and progression-free survival than those with higher Beclin 1 expression. Thus, our data demonstrated that low expression of Beclin 1, associated with high Bcl-xL, played as an independent biomarker, contributing to a more aggressive cancer cell phenotype and poor prognosis for gastric tumor.