mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants

Int J Mol Sci. 2018 Oct 30;19(11):3396. doi: 10.3390/ijms19113396.


Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan®-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20⁺/KRT5-, 5-year DSS 0%, p < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20⁺/KRT- tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested).

Keywords: Bladder cancer; KRT20; KRT5; molecular diagnostics; molecular subtyping; muscle-invasive bladder cancer.

MeSH terms

  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Keratin-20 / biosynthesis
  • Keratin-5 / biosynthesis*
  • Male
  • Neoplasm Proteins / biosynthesis*
  • RNA, Messenger / biosynthesis*
  • RNA, Neoplasm / biosynthesis*
  • Survival Rate
  • Urinary Bladder Neoplasms* / metabolism
  • Urinary Bladder Neoplasms* / mortality
  • Urinary Bladder Neoplasms* / pathology
  • Urothelium / metabolism*
  • Urothelium / pathology


  • KRT20 protein, human
  • KRT5 protein, human
  • Keratin-20
  • Keratin-5
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm