摘要

  背景多项研究表明，自噬参与了食管腺癌（EAC）的发生过程。本研究的目的是探索与 EAC 患者总生存期 (OS) 相关的自噬相关基因 (ARG)。方法从TCGA数据库下载EAC和正常样本中ARGs的表达。 GO和KEGG富集分析用于研究ARGs生物信息学功能。进行单变量和多变量 cox 回归以确定预后 ARG 和独立危险因素。建立ROC曲线以评估预测预后的可行性。最后，进一步探讨了 ARG 与临床特征之间的相关性。此外，在 EAC 标本和正常食管黏膜组织中证实了显着不同的 ARG。结果从 EAC 和正常组织中选择了 30 种显着不同的 ARG。功能富集表明这些 ARGs 主要与细胞凋亡有关。多变量 cox 回归分析表明，8 个 ARG 与 OS 显着相关。在这8个基因中，BECN1（HR = 0.321，P= 0.046）、DAPK1（HR = 0.636，P= 0.025）和CAPN1（HR = 0.395，P= 0.004）在生存中起保护作用。性别（HR = 0.225，P= 0.032）、分期（HR = 5.841，P= 0.008）和风险评分（HR = 1.131，P < 0.001）是独立的预后危险因素。 ROC 曲线显示出使用风险评分预测生存的更好效果。此外，我们发现 BECN1、DAPK1、VAMP7 和 SIRT1 基因与生存状态、性别、原发肿瘤和肿瘤分期显着相关（均 P < 0.05）。实验结果证实，与正常食管黏膜组织相比，EAC组织中BIRC5过表达，ITPR1、PRKN下调（均P < 0.05）。结论我们的研究结果表明自噬参与了 EAC 的过程。几种 ARG 可能可以作为诊断和预后生物标志物，并可能有助于促进 EAC 患者的治疗目标。

  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.

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07416-w