title: Prognostic significance of autophagy-related proteins expression in resected human gastric adenocarcinoma.
abstract: Gastric adenocarcinoma (GC) is one of the most common malignancies in the world and one of the most frequent causes of cancer-related death. Autophagy is a highly regulated catabolic pathway responsible for the degradation of long-lived proteins and damaged intracellular organelles. However, the mechanism and guiding significance of autophagy in the development and progression of GC have remained to be elucidated. This study aimed to explore the clinicopathological significances and prognostic values of autophagy-related proteins AMBRA1 and Beclin-1 in GC. Quantum dots based immunofluorescence histochemistry (QDs-IHC) was performed to observe the expression of AMBRA1 and Beclin-1 proteins in the tissue microarrays including 163 specimens of GC and 20 noncancerous gastric tissues. Simultaneously, AMBRA1 and Beclin-1 proteins were detected by Western blotting in the 10 fresh GC and corresponding normal gastric tissues. The results showed that the expression levels of both AMBRA1 and Beclin-1 proteins were higher in GC tissues than in noncancerous gastric tissues by QDs-IHC and Western blotting (P<0.05). High AMBRA1 expression was detected in 90 of 163 (55.2%) GCs and high Beclin-1 expression was detected in 83 of 163 (50.9%) GCs. High AMBRA1 expression was closely related to depth of invasion, and lymph nodes metastasis (P<0.05). High expression of Beclin-1 protein was correlated with tumor grade (P<0.05). Positive correlation was observed between AMBRA1 and Beclin-1. Survival analysis indicated the high expression of AMBRA1 and Beclin- 1 was an independent factor in predicting poor overall survival (OS) of GC patients. These findings suggest the high expression of AMBRA1 and Beclin-1 proteins is significantly correlated with GC progression. High AMBRA1 and Beclin-1 expression heralds worse outcome of GC patients, suggesting a novel candidate prognostic marker and a therapeutic target for GC.
authors.affiliation: Department of General Surgery, China Resources & WISCO General Hospital, Wuhan, 430080, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Qu
authors.affiliation: Department of General Surgery, China Resources & WISCO General Hospital, Wuhan, 430080, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Pathology, China Resources & WISCO General Hospital, Wuhan, 430080, China.
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Ma
authors.affiliation: Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, 430071, China.
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Science and Education, China Resources & WISCO General Hospital, Wuhan, 430080, China. 18483863@qq.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, China Resources & WISCO General Hospital, Wuhan, 430080, China. 1134183435@qq.com.
authors.forename: Jiang
authors.initials: J
authors.lastname: Xie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001343:Autophagy; D000071186:Beclin-1 / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D046888:Tissue Array Analysis / Q000379:methods; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C553334:AMBRA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C491997:BECN1 protein, human; D000071186:Beclin-1
keywords: AMBRA1; Beclin-1; autophagy; gastric carcinoma; prognosis