Autophagic protein Beclin 1 serves as an independent positive prognostic biomarker for non-small cell lung cancer.

Autophagic protein Beclin 1 serves as an independent positive prognostic biomarker for non-small cell lung cancer.
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自噬蛋白 Beclin 1 作为非小细胞肺癌的独立阳性预后生物标志物

DOI:
10.1371/journal.pone.0080338
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Liu A
Liu A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhou W;Yue C;Deng J;Hu R;Xu J;Feng L;Lan Q;Zhang W;Ji D;Wu J;Liu Q;Liu A

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Beclin 1是自噬的关键调节因子,已被发现在多种人类恶性肿瘤中异常表达。本研究采用免疫组化(IHC)方法检测Beclin 1蛋白在非小细胞肺癌(NSCLC)及配对的正常邻近肺组织中的表达,并分析其在NSCLC中的临床病理/预后意义。利用受试者工作特征(ROC)曲线分析确定训练集(n = 105) Beclin 1表达的截断点(>2 VS.≤2)。为了验证roc衍生的截止值,在测试集(n = 111)和整体患者队列(n = 216)中分析Beclin 1与患者临床特征和结局的关系。我们的数据显示,Beclin 1在非小细胞肺癌组织中的表达明显低于邻近正常组织,与肿瘤复发率呈负相关(65.8% VS 32.3%, p < 0.001)。在测试集和整体患者队列中,Beclin 1低表达与Beclin 1高表达相比,总生存期(OS) (p < 0.001)和无进展生存期(PFS) (p < 0.001)明显低于。在测试集和整体患者队列中,Beclin 1高表达和低表达患者的中位OS持续时间分别为108对24.5个月(p < 0.001)和108对28个月(p < 0.001)。此外,Beclin 1的低表达也是NSCLC患者各阶段预后不良的因素。多因素分析表明Beclin 1是NSCLC的独立预后因素。我们在本研究中的发现提供了证据,证明Beclin 1可能因此在未来成为这种肿瘤实体的独立预后生物标志物。
Beclin 1, a key regulator of autophagy, has been found to be aberrantly expressed in a variety of human malignancies. Herein, we employed immunohistochemistry (IHC) to detect the protein expression of Beclin 1 in non-small cell lung cancer (NSCLC) and paired normal adjacent lung tissues, and analyzed its clinicopathological/prognostic significance in NSCLC. Receiver operating characteristic (ROC) curve analysis was utilized to determine a cutoff point (>2 VS. ≤2) for Beclin 1 expression in a training set (n = 105). For validation, the ROC-derived cutoff value was subjected to analysis of the association of Beclin 1 with patients’ clinical characteristics and outcome in a testing set (n = 111) and the overall patient cohort (n = 216). Our data showed that Beclin 1 was significantly lower in NSCLC tissues compared with the adjacent normal tissues, negatively associating with tumor recurrence rate (65.8% VS 32.3%; p < 0.001). In the testing set and the overall patient cohort, low expression of Beclin 1 showed significantly inferior overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) compared to high expression of Beclin 1. In the testing set and the overall patient cohort, the median duration of OS for patients with high and low expression of Beclin 1 was 108 VS. 24.5 months (p < 0.001) and 108 VS. 28 months (p < 0.001), respectively. Furthermore, low expression of Beclin 1 was also a poor prognostic factor within each stage of NSCLC patients. Multivariate analysis identified that Beclin 1 was an independent prognostic factor for NSCLC. Our findings in the present study provided evidence that Beclin 1 may thus emerge as an independent prognostic biomarker in this tumor entity in the future.
DOI: 10.1101/gad.1545107
发表时间: 2007-06-01
影响因子: 10.5
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发表时间: 2012
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DOI: 10.4161/auto.5.3.7658
发表时间: 2009-04-01
期刊: AUTOPHAGY
影响因子: 13.3
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