Profiles of autophagy-related genes in esophageal adenocarcinoma

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RESEARCH ARTICLE

Open Access

Profiles of autophagy-related genes in esophageal adenocarcinoma Lei Zhu1,2†, Lin Dong1,2†, Minghao Feng1,2†, Fugui Yang1,2, Wenhao Jiang1,2, Zhiyuan Huang1,2, Fabing Liu2,3, Lingwei Wang1,2, Guangxue Wang2* and Qinchuan Li1,2*

Abstract Background: Several studies have demonstrated autophagy was involved in the process of esophageal adenocarcinoma (EAC). The aim of this study was to explore autophagy-related genes (ARGs) correlated with overall survival (OS) in EAC patients. Methods: Expressions of ARGs in EAC and normal samples were downloaded from TCGA database. GO and KEGG enrichment analyses were used to investigate the ARGs bioinformatics functions. Univariate and multivariate cox regressions were performed to identify prognostic ARGs and the independent risk factors. ROC curve was established to evaluate the feasibility to predict the prognosis. Finally, the correlations between ARGs and clinical features were further explored. In addition, significantly different ARGs were verified in EAC specimens and normal esophageal mucosal tissues. Results: Thirty significantly different ARGs were selected from EAC and normal tissues. Functional enrichments showed these ARGs were mainly related apoptosis. Multivariate cox regression analyses demonstrated eight ARGs were significantly associated with OS. Among these eight genes, BECN1 (HR = 0.321, P = 0.046), DAPK1 (HR = 0.636, P = 0.025) and CAPN1 (HR = 0.395, P = 0.004) played protective roles in survival. Gender (HR = 0.225, P = 0.032), stage (HR = 5.841, P = 0.008) and risk score (HR = 1.131, P < 0.001) were independent prognostic risk factors. ROC curves showed better efficacy to predict survival using the risk score. Additionally, we found BECN1, DAPK1, VAMP7 and SIRT1 genes were correlated significantly with survival status, gender, primary tumor and tumor stage (all P < 0.05). The experimental results confirmed the BIRC5 was overexpressed and the ITPR1, PRKN were downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P < 0.05). Conclusion: Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients. Keywords: Autophagy, Esophageal adenocarcinoma, Prognosis

* Correspondence: [email protected]; [email protected] † Lei Zhu, Lin Dong and Minghao Feng contributed equally to this work. 2 Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China 1 Department of Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as l