Construction and Evaluation of a Risk Score Model for Autophagy-Related Genes in Esophageal Adenocarcinoma

Med Sci Monit. 2021 Jan 29:27:e927850. doi: 10.12659/MSM.927850.

Abstract

BACKGROUND Several studies have suggested the importance of autophagy during esophageal adenocarcinoma (EAC) development. This study aimed to explore the autophagy-related genes correlated with overall survival in patients with EAC. MATERIAL AND METHODS The RNA-seq expression profiles and clinical data of patients with EAC were screened using The Cancer Genome Atlas (TCGA) database. Screening of autophagy-related genes was conducted using the human autophagy database (HADb). Bioinformatic analysis was conducted and included the following: univariate cox, lasso regression, and multivariate cox regression analysis; building overall survival assessment of the prognosis model; drawing the model of receiver operating characteristic (ROC) curve and determining the area under the curve; and a C-index reliability index assessment model through Kaplan-Meier screening of statistically significant genes in the model. The screening results were verified via Oncomine differential expression analysis. Gene set enrichment analysis (GSEA) was further used to analyze the molecular biological functions and related pathways of the gene model. RESULTS Through cox regression and ROC analysis, the model showed that the risk score could accurately and independently predict the prognosis of EAC. The screening identified 4 genes: DAPK1, BECN1, ATG5, and VAMP7. GSEA showed that the high and low expression levels of the 4 genes were mainly enriched in biological functions, such as cell production and regulation, and metabolic pathways that maintain cell activity. CONCLUSIONS Our research found that autophagy was involved in the process of EAC development and that several autophagy-related genes may provide prognostic information and clinical application value for patients with EAC.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Autophagy / genetics*
  • Autophagy-Related Protein 5 / genetics
  • Beclin-1 / genetics
  • Biomarkers, Tumor / genetics
  • Computational Biology / methods*
  • Databases, Genetic
  • Death-Associated Protein Kinases / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / mortality
  • Gene Expression / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Prognosis
  • R-SNARE Proteins / genetics
  • ROC Curve
  • Reproducibility of Results
  • Risk Factors
  • Transcriptome / genetics

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • BECN1 protein, human
  • Beclin-1
  • Biomarkers, Tumor
  • R-SNARE Proteins
  • VAMP7 protein, human
  • DAPK1 protein, human
  • Death-Associated Protein Kinases

Supplementary concepts

  • Adenocarcinoma Of Esophagus