Screening a Prognosis-Related Target Gene in Patients with HER-2-Positive Breast Cancer by Bioinformatics Analysis

Med Princ Pract. 2021;30(4):376-384. doi: 10.1159/000516322. Epub 2021 Apr 6.

Abstract

Objective: The objective of the present study was to determine a target gene and explore the molecular mechanisms involved in the pathogenesis of HER-2-positive breast cancer.

Methods: Three RNA expression profiles obtained from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) were used to identify differentially expressed genes (DEGs) using the R software. A protein-protein interaction network was then constructed, and hub genes were determined. Subsequently, the relationship between clinical parameters and hub genes was examined to screen for target genes. Next, DNA methylation and genomic alterations of the target gene were evaluated. To further explore potential molecular mechanisms, a functional enrichment analysis of genes coexpressed with the target gene was performed.

Results: The differential expression analysis revealed 217 DEGs in HER-2-positive breast cancer samples compared to normal breast tissues. RRM2 was the only hub gene closely associated with lymphatic metastasis and the patients' prognosis. Additionally, RRM2 was found to be consistently amplified and negatively associated with the level of methylation. Functional enrichment analysis showed that the coexpressed genes were mainly involved in cell cycle regulation.

Conclusions: RRM2 was identified as a target gene associated with the initiation, progression, and prognosis of HER-2-positive breast cancer, which may be considered as a new biomarker and therapeutic target.

Keywords: Bioinformatics analysis; Differentially expressed genes; HER-2-positive breast cancer; RRM2; Target genes.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Computational Biology*
  • DNA Methylation
  • Early Detection of Cancer
  • Female
  • Gene Expression Profiling / methods*
  • Genomics
  • Humans
  • Lymphatic Metastasis / genetics*
  • Middle Aged
  • Prognosis
  • Receptor, ErbB-2
  • Ribonucleoside Diphosphate Reductase / genetics*
  • Survival Analysis

Substances

  • ribonucleotide reductase M2
  • Ribonucleoside Diphosphate Reductase
  • ERBB2 protein, human
  • Receptor, ErbB-2