Molecular characterization of low grade and high grade bladder cancer

PLoS One. 2019 Jan 16;14(1):e0210635. doi: 10.1371/journal.pone.0210635. eCollection 2019.


Background: Bladder cancer (BC) is the 9th most common cancer diagnosis worldwide. Low grade (LG) represents 70% of all BCs, characterized by recurrence and rare ability (10-15%) to progress to high grade (HG) and invade. The remaining 30% is high grade (HG), fast invasive BC, which is resistant to therapy. Identifying biomarkers for predicting those tumors able to progress is a key goal for patient outcome improvement. This study focuses on the most promising prognostic markers.

Materials and methods: TP53 and FGFR3 mutational status, Survivin, CK19, CK20, E-cadherin and CD44 gene expression analysis were performed on 66 BCs.

Results: Survivin was found associated to tumor grade (p<0.05). Moreover, Survivin correlated with CD44 in TP53 wild type (p = 0.0242) and FGFR3 wild type (p = 0.0036) tumors. In particular the Survivin-CD44 correlation was associated to HG FGFR3 wild type BCs (p = 0.0045). Unsupervised hierarchical clustering based on gene expression data identified four distinct molecular groups reflecting the patient histology (p = 0.038).

Conclusion: We suggest Survivin, both as a biomarker associated to G3 BCs but negatively related to TP53 mutational status, and as a potential novel therapeutic target.

MeSH terms

  • Aged
  • Cadherins / genetics
  • DNA Mutational Analysis / methods
  • Female
  • Humans
  • Hyaluronan Receptors / genetics
  • Keratin-20 / genetics
  • Male
  • Mutation / genetics
  • Neoplasm Grading
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Survivin / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*


  • Cadherins
  • Hyaluronan Receptors
  • KRT20 protein, human
  • Keratin-20
  • Survivin
  • Tumor Suppressor Protein p53
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3

Grants and funding

The authors received no specific funding for this work.