Prognostic Significance of Autophagy-Related Protein Expression in Resected Pancreatic Ductal Adenocarcinoma
Prognostic Significance of Autophagy-Related Protein Expression in Resected Pancreatic Ductal Adenocarcinoma
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DOI：
10.1097/mpa.0b013e318279d0dc
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发表时间：
2013-07-01
期刊：
影响因子：
2.9
通讯作者：
Lee, Myung Ah
中科院分区：
文献类型：
--
作者：
Ko, Yoon Ho;Cho, Young-Seok;Lee, Myung Ah
目的：自噬是清除聚集蛋白和受损细胞器的关键途径。本研究旨在探讨自噬相关蛋白在切除胰腺导管腺癌(PDAC)患者临床预后中的作用。方法：采用免疫组织化学方法检测73例胰腺导管腺癌组织中5种自噬相关蛋白的表达。结果：73例肺癌组织中，ATG5、Ambra1、Beclin-1、LC3B和BIF-1的表达频率分别为49.3%(36/73)、63.9%(46/72)、47.9%(35/73)、83.3%(60/72)和69.9%(51/73)。在所有蛋白对中，自噬相关蛋白的表达之间存在显著相关性。T分期晚期与较多的蛋白质改变有关(P=0.059)。多因素分析显示，Beclin-1过度表达和自噬相关蛋白改变增加与预后不良独立相关(风险比分别为5.365，P=0.001和5.270，P=0.022)。结论：自噬相关蛋白的获得与临床预后不良有关。自噬的检测和抑制为PDAC提供了一个潜在的治疗靶点。
Objectives: Autophagy is a critical intracellular pathway for the removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins to clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC).Methods: The expression of 5 autophagy-related proteins in the PDAC tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins.Results: Of the 73 patients, autophagy-related protein expression frequencies were 49.3% (36/73) for Atg5, 63.9% (46/72) for Ambra1, 47.9% (35/73) for beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was significant for all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (P = 0.059). Multivariate analysis revealed that beclin-1 overexpression and increases in the alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio of 5.365, P = 0.001 and hazard ratio of 5.270, P = 0.022, respectively).Conclusions: The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The detection and inhibition of autophagy offers a potential therapeutic target for PDAC.