Assessment of Luminal and Basal Phenotypes in Bladder Cancer

Sci Rep. 2020 Jun 16;10(1):9743. doi: 10.1038/s41598-020-66747-7.

Abstract

Genomic profiling studies have demonstrated that bladder cancer can be divided into two molecular subtypes referred to as luminal and basal with distinct clinical behaviors and sensitivities to frontline chemotherapy. We analyzed the mRNA expressions of signature luminal and basal genes in bladder cancer tumor samples from publicly available and MD Anderson Cancer Center cohorts. We developed a quantitative classifier referred to as basal to luminal transition (BLT) score which identified the molecular subtypes of bladder cancer with 80-94% sensitivity and 83-93% specificity. In order to facilitate molecular subtyping of bladder cancer in primary care centers, we analyzed the protein expressions of signature luminal (GATA3) and basal (KRT5/6) markers by immunohistochemistry, which identified molecular subtypes in over 80% of the cases. In conclusion, we provide a tool for assessment of molecular subtypes of bladder cancer in routine clinical practice.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Transitional Cell / pathology
  • Databases, Genetic
  • GATA3 Transcription Factor / analysis
  • GATA3 Transcription Factor / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunohistochemistry / methods
  • Keratin-5 / analysis
  • Keratin-5 / genetics
  • Keratin-6 / analysis
  • Keratin-6 / genetics
  • Phenotype
  • Prognosis
  • Sensitivity and Specificity
  • Urinary Bladder Neoplasms / classification*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • KRT5 protein, human
  • KRT6A protein, human
  • Keratin-5
  • Keratin-6