Prognostic value of autophagy related proteins ULK1, Beclin 1, ATG3, ATG5, ATG7, ATG9, ATG10, ATG12, LC3B and p62/SQSTM1 in gastric cancer.

Autophagy-related (ATG) genes contributed to tumorigenesis and cancer progression. This study aims to investigate the expression of ATG proteins and their clinicopathological significance in gastric cancer. Nine well-known ATG proteins, (ULK1, Beclin 1, ATG3, ATG5, ATG7, ATG9, ATG10, ATG12 and LC3B) and p62/SQSTM1, which represented key regulators that participated in whole autophagosomes stepwise processes, were detected in a large cohort of 352 primary gastric cancer patients. Among these 352 patients, 117 cases were randomly assigned to the training set to detect the clinicopathological value of ATG proteins, and another 235 patients were used as the testing set for further validation. Except for Beclin 1, ATG9 and ATG10, another six ATG proteins and p62/SQSTM1 were closely correlated with histological types for gastric cancer. Moreover, low expression of ULK1, Beclin 1 and ATG10 were associated with lymph node metastasis. In addition, down-regulation of ULK1, Beclin 1, ATG7 and ATG10, up-regulation of ATG12 correlated with advanced TNM stage. Importantly, multivariate cox analysis identified ULK1, Beclin 1, ATG3 and ATG10 as favorable independent prognostic factors for overall survival. Combination analysis of ULK1, Beclin 1, ATG3, ATG10 revealed the improved prognostic accuracy for gastric cancer. Our study showed that ATG proteins might serve as novel prognostic biomarkers in gastric cancer, and supply a new valuable insight into cancer treatment targeting autophagy for patients.