A glycolysis-related gene expression signature in predicting recurrence of breast cancer

Aging (Albany NY). 2020 Nov 16;12(24):24983-24994. doi: 10.18632/aging.103806. Epub 2020 Nov 16.

Abstract

Metabolic change is the hallmark of cancer. In the present study, we aimed to develop a glycolysis-related gene signature to predict the prognosis of breast cancer patients. Gene expression profiles and clinical data of breast cancer patients were obtained from the GEO database. A four-gene based signature (ALDH2, PRKACB, STMN1 and ZNF292) was developed to separate patients into high-risk and low-risk groups. Patients in the low-risk group had significantly better prognosis than those in the high-risk group. Time-dependent ROC analysis demonstrated that the glycolysis-related gene signature had excellent prognostic accuracy. We further confirmed the expression of the four prognostic genes in breast cancer and paracancerous tissue samples using qRT-PCR analysis. Expression level of PRKACB was higher in paracancerous tissues, while STMN1 and ZNF292 were overexpressed in tumor samples, no significant difference was observed in ALDH2 expression level. Global proteome data of 105 TCGA breast cancer samples obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to evaluate the prognostic value in protein levels. Consistently, high expression level of PRKACB protein was associated with favorable prognosis, while high ZNF292 and STMN1 protein expression levels indicated poor prognosis. The glycolysis-related gene signature might provide an effective prognostic predictor and a new insight for individualize management of breast cancer patients.

Keywords: breast cancer; glycolysis; prognosis.

MeSH terms

  • Aldehyde Dehydrogenase, Mitochondrial / genetics*
  • Aldehyde Dehydrogenase, Mitochondrial / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / genetics*
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / metabolism
  • Databases, Genetic
  • Female
  • Glycolysis / genetics*
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Staging
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Prognosis
  • Proportional Hazards Models
  • Proteomics
  • Reproducibility of Results
  • Risk Assessment
  • Stathmin / genetics*
  • Stathmin / metabolism
  • Transcriptome*

Substances

  • Carrier Proteins
  • Nerve Tissue Proteins
  • STMN1 protein, human
  • Stathmin
  • ZNF292 protein, human
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase, Mitochondrial
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
  • PRKACB protein, human