Department of Hematology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Autophagy. 2012 Mar;8(3):389-400. doi: 10.4161/auto.18641. Epub 2012 Jan 19.
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.
最近的研究表明,自噬失调在肿瘤发生中起着关键作用。在这里,我们确定了自噬相关蛋白 Beclin 1 在胃癌中的预后价值。对 153 名原发性胃癌患者进行了 Beclin 1 表达和生存预后分析。其中,随机分配 68 名患者作为训练集,通过接受工作特征 (ROC) 曲线分析生成 Beclin 1 表达的截断分数。ROC 生成的截断分数用于分析 Beclin 1 与临床特征和患者预后的关系。在测试集 (n=85) 和所有患者 (n=153) 中,单因素和多因素分析均发现 Beclin 1 的低表达预测胃癌患者的总生存期和无进展生存期不良。此外,在胃癌患者的每个分期中,Beclin 1 表达均是 II 期、III 期和 IV 期患者的预后指标。重要的是,证明了 Beclin 1 和 Bcl-xL 表达之间存在反向关系。在 Bcl-xL 表达升高的患者中,Beclin 1 表达较低的亚组的总生存期和无进展生存期比 Beclin 1 表达较高的亚组差。因此,我们的数据表明,Beclin 1 表达水平低,与 Bcl-xL 高表达相关,作为一个独立的生物标志物,与更具侵袭性的癌细胞表型和不良的胃癌预后相关。