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      Prognostic significance of autophagy-related protein expression in resected pancreatic ductal adenocarcinoma.

      Pancreas
      Adaptor Proteins, Signal Transducing, metabolism, Adenocarcinoma, pathology, surgery, Adult, Aged, Aged, 80 and over, Apoptosis Regulatory Proteins, Autophagy, Carcinoma, Pancreatic Ductal, Female, Humans, Immunohistochemistry, Male, Membrane Proteins, Microtubule-Associated Proteins, Middle Aged, Multivariate Analysis, Neoplasm Staging, Pancreatic Neoplasms, Prognosis, Proteins, Survival Analysis, Tissue Array Analysis

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          Abstract

          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). 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. 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). 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.

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