Identification of prognostic biomarkers for breast cancer based on miRNA and mRNA co-expression network

J Cell Biochem. 2019 Sep;120(9):15378-15388. doi: 10.1002/jcb.28805. Epub 2019 Apr 29.

Abstract

Purpose: Breast cancer (BC) remains a serious health threat for women due to its high incidence and the trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) could play important roles in various biological processes involved in the pathogenesis of BC. The present study aimed to identify potential prognostic biomarkers associated with BC.

Methods: Here, original gene expression profiles of patients with BC was downloaded from The Cancer Genome Atlas (TCGA) database. TargetScan, miRDB, and miRTarBase databases were used to predict the target genes of prognostic-related differentially expressed miRNAs (DEMs). Subsequently, functional enrichment analysis and topological analysis were performed on the overlaps of target genes and differentially expressed mRNAs (DEGs), and Kaplan-Meier analysis was used to predict prognosis-related target genes to identify prognostic biomarkers.

Results: A total of 218 DEMs and 2222 DEGs were extracted in which eight miRNAs were associated with prognosis, and 278 target DEGs were screened out incorporated into functional enrichment analysis and protein-protein interaction network visualization studies. Additionally, five hub genes (CXCL12, IGF1, LEF1, MMP1, and RACGAP1) were observed as potential biomarkers for BC prognosis through survival analysis.

Conclusion: We performed a distinctive correlation analysis of miRNA-mRNA in BC patients, and identified eight miRNAs and five hub genes may be effective biomarkers for the prognosis of BC patients.

Keywords: biomarkers; breast cancer; hub genes; miRNA-mRNAco-expression network; protein-protein interaction network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics*
  • Chemokine CXCL12 / genetics
  • Female
  • GTPase-Activating Proteins / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Lymphoid Enhancer-Binding Factor 1 / genetics
  • Matrix Metalloproteinase 1 / genetics
  • MicroRNAs / genetics*
  • Prognosis
  • RNA, Messenger / genetics
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • CXCL12 protein, human
  • Chemokine CXCL12
  • GTPase-Activating Proteins
  • IGF1 protein, human
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • MicroRNAs
  • RNA, Messenger
  • mgcRacGAP
  • Insulin-Like Growth Factor I
  • MMP1 protein, human
  • Matrix Metalloproteinase 1