The expression characteristics and prognostic roles of autophagy-related genes in gastric cancer

PeerJ

Hao Li¹  Jingwei Liu²  Mengya Wang³  Jingjing Jing³  Liping Sun³  Yuan Yuan³ 

[1] Department of Clinical Laboratory, the First Hospital of China Medical University, Shenyang, China;Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, China;Tumor Etiology and Screening Department of Cancer Institute, and Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, China;

关键词: Autophagy;    Gastric cancer;    Gene expression;    TCGA;    ATG4;   

DOI  :  10.7717/peerj.10814

来源: DOAJ

【 摘 要 】

Background Autophagy is an evolutionally highly conserved process, accompanied by the dynamic changes of various molecules, which is necessary for the orderly degradation and recycling of cellular components. The aim of the study was to identify the role of autophagy-related (ATG) genes in the occurrence and development of gastric cancer (GC). Methods Data from Oncomine dataset was used for the differential expression analysis between cancer and normal tissues. The association of ATG genes expression with clinicopathologic indicators was evaluated by The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Moreover, using the TCGA datasets, the prognostic role of ATG genes was assessed. A nomogram was further built to assess the independent prognostic factors. Results The expression of autophagy-related genes AMBRA1, ATG4B, ATG7, ATG10, ATG12, ATG16L2, GABARAPL2, GABARAPL1, ULK4 and WIPI2 showed differences between cancer and normal tissues. After verification, ATG14 and ATG4D were significantly associated with TNM stage. ATG9A, ATG2A, and ATG4D were associated with T stage. VMP1 and ATG4A were low-expressed in patients without lymph node metastasis. No gene in autophagy pathway was associated with M stage. Further multivariate analysis suggested that ATG4D and MAP1LC3C were independent prognostic factors for GC. The C-index of nomogram was 0.676 and the 95% CI was 0.628 to 0.724. Conclusion Our study provided a comprehensive illustration of ATG genes expression characteristics in GC. Abnormal expressions of the ubiquitin-like conjugated system in ATG genes plays a key role in the occurrence of GC. ATG8/LC3 sub-system may play an important role in development and clinical outcome of GC. In the future, it is necessary to further elucidate the alterations of specific ATG8/LC3 forms in order to provide insights for the discovery, diagnosis, or targeting for GC.

【 授权许可】

Unknown