Low expression of Beclin 1, associated with high Bcl-xL, predicts a malignant phenotype and poor prognosis of gastric cancer
Low expression of Beclin 1, associated with high Bcl-xL, predicts a malignant phenotype and poor prognosis of gastric cancer
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Beclin 1 的低表达与高 Bcl-xL 相关，可预测胃癌的恶性表型和不良预后
DOI：
10.4161/auto.18641
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发表时间：
2012-03-01
期刊：
影响因子：
13.3
通讯作者：
Liu, Quentin
中科院分区：
文献类型：
--
作者：
Zhou, Wei-Hua;Tang, Fang;Liu, Quentin
最近的研究表明，自噬的失调在肿瘤的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例原发胃癌患者进行Beclin-1基因表达和生存预后分析。其中68例患者被随机分配并作为训练集，通过接收操作特征(ROC)曲线分析生成Beclin-1表达的截止值。采用ROC分界值分析Beclin 1与临床特征和患者预后的关系。在一组测试组(n=85)和全部患者(n=153)中，单变量和多变量分析都发现Beclin 1的低表达预示着胃癌患者不利的总体生存和无进展生存。此外，在胃癌各期患者中，Beclin 1的表达是II、III、IV期患者的预后指标。重要的是，Beclin 1与Bclxl的表达呈负相关。在Bclxl高表达的患者中，Beclin 1低表达的患者的总体生存期和无进展生存期低于Beclin 1高表达的患者。因此，我们的数据表明，Beclin 1的低表达与高Bclxl相关，是一个独立的生物标志物，有助于更具侵袭性的癌细胞表型和较差的胃癌预后。
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.