Weighted gene co-expression network analysis of gene modules for the prognosis of esophageal cancer

J Huazhong Univ Sci Technolog Med Sci. 2017 Jun;37(3):319-325. doi: 10.1007/s11596-017-1734-8. Epub 2017 Jun 6.

Abstract

Esophageal cancer is a common malignant tumor, whose pathogenesis and prognosis factors are not fully understood. This study aimed to discover the gene clusters that have similar functions and can be used to predict the prognosis of esophageal cancer. The matched microarray and RNA sequencing data of 185 patients with esophageal cancer were downloaded from The Cancer Genome Atlas (TCGA), and gene co-expression networks were built without distinguishing between squamous carcinoma and adenocarcinoma. The result showed that 12 modules were associated with one or more survival data such as recurrence status, recurrence time, vital status or vital time. Furthermore, survival analysis showed that 5 out of the 12 modules were related to progression-free survival (PFS) or overall survival (OS). As the most important module, the midnight blue module with 82 genes was related to PFS, apart from the patient age, tumor grade, primary treatment success, and duration of smoking and tumor histological type. Gene ontology enrichment analysis revealed that "glycoprotein binding" was the top enriched function of midnight blue module genes. Additionally, the blue module was the exclusive gene clusters related to OS. Platelet activating factor receptor (PTAFR) and feline Gardner-Rasheed (FGR) were the top hub genes in both modeling datasets and the STRING protein interaction database. In conclusion, our study provides novel insights into the prognosis-associated genes and screens out candidate biomarkers for esophageal cancer.

Keywords: The Cancer Genome Atlas; co-expression network analysis; enrichment analysis; esophageal cancer; weighted gene co-expression network analysis.

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Antineoplastic Agents / therapeutic use
  • Atlases as Topic
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Databases, Genetic
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / mortality
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Ontology
  • Gene Regulatory Networks
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Microarray Analysis
  • Multigene Family
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Platelet Membrane Glycoproteins / genetics*
  • Platelet Membrane Glycoproteins / metabolism
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • Survival Analysis
  • src-Family Kinases / genetics*
  • src-Family Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Platelet Membrane Glycoproteins
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • platelet activating factor receptor
  • proto-oncogene proteins c-fgr
  • src-Family Kinases