Systematic prediction of key genes for ovarian cancer by co-expression network analysis

J Cell Mol Med. 2020 Jun;24(11):6298-6307. doi: 10.1111/jcmm.15271. Epub 2020 Apr 21.

Abstract

Ovarian cancer (OC) is the most lethal gynaecological malignancy, characterized by high recurrence and mortality. However, the mechanisms of its pathogenesis remain largely unknown, hindering the investigation of the functional roles. This study sought to identify key hub genes that may serve as biomarkers correlated with prognosis. Here, we conduct an integrated analysis using the weighted gene co-expression network analysis (WGCNA) to explore the clinically significant gene sets and identify candidate hub genes associated with OC clinical phenotypes. The gene expression profiles were obtained from the MERAV database. Validations of candidate hub genes were performed with RNASeqV2 data and the corresponding clinical information available from The Cancer Genome Atlas (TCGA) database. In addition, we examined the candidate genes in ovarian cancer cells. Totally, 19 modules were identified and 26 hub genes were extracted from the most significant module (R2 = .53) in clinical stages. Through the validation of TCGA data, we found that five hub genes (COL1A1, DCN, LUM, POSTN and THBS2) predicted poor prognosis. Receiver operating characteristic (ROC) curves demonstrated that these five genes exhibited diagnostic efficiency for early-stage and advanced-stage cancer. The protein expression of these five genes in tumour tissues was significantly higher than that in normal tissues. Besides, the expression of COL1A1 was associated with the TAX resistance of tumours and could be affected by the autophagy level in OC cell line. In conclusion, our findings identified five genes could serve as biomarkers related to the prognosis of OC and may be helpful for revealing pathogenic mechanism and developing further research.

Keywords: autophagy; ovarian cancer; prognosis; taxol (TAX) resistance; weighted gene co-expression network analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Ontology
  • Gene Regulatory Networks*
  • Genes, Neoplasm*
  • Humans
  • Kaplan-Meier Estimate
  • Ovarian Neoplasms / genetics*
  • Progression-Free Survival
  • Protein Interaction Maps / genetics
  • Reproducibility of Results

Substances

  • Collagen Type I
  • Collagen Type I, alpha 1 Chain

Associated data

  • GENBANK/GSM38087
  • GENBANK/GSM231870
  • GENBANK/GSM152673
  • GENBANK/GSM277697
  • GENBANK/GSM277737
  • GENBANK/GSM277738
  • GENBANK/GSM301703
  • GENBANK/GSM102478
  • GENBANK/GSM102483
  • GENBANK/GSM88956
  • GENBANK/GSM102426
  • GENBANK/GSM46830
  • GENBANK/GSM53029
  • GENBANK/GSM53054
  • GENBANK/GSM152581
  • GENBANK/GSM203626
  • GENBANK/GSM88974
  • GENBANK/GSM102445
  • GENBANK/GSM46831
  • GENBANK/GSM53036
  • GENBANK/GSM152577
  • GENBANK/GSM88973
  • GENBANK/GSM76600