Expression of proteins FGFR3, PI3K, AKT, p21Waf1/Cip1 and cyclins D1 and D3 in patients with T1 bladder tumours: clinical implications and prognostic significance

Actas Urol Esp. 2017 Apr;41(3):172-180. doi: 10.1016/j.acuro.2016.09.003. Epub 2016 Oct 7.
[Article in English, Spanish]

Abstract

Objective: To determine the differential protein expression of biomarkers FGFR3, PI3K (subunits PI3Kp110α, PI3KClassIII, PI3Kp85), AKT, p21Waf1/Cip1 and cyclins D1 and D3 in T1 bladder cancer versus healthy tissue and to study their potential role as early recurrence markers.

Material and method: This is a prospective study that employed a total of 67 tissue samples (55 cases of T1 bladder tumours that underwent transurethral resection and 12 cases of adjacent healthy mucosa). The protein expression levels were assessed using Western blot, and the means and percentages were compared using Student's t-test and the chi-squared test. The survival analysis was conducted using the Kaplan-Meier method and the log-rank test.

Results: Greater protein expression was detected for FGFR3, PI3Kp110α, PI3KClassIII, cyclins D1 and D3 and p21Waf1/Cip1 in the tumour tissue than in the healthy mucosa. However, these differences were not significant for PI3Kp85 and AKT. We observed statistically significant correlations between early recurrence and PI3Kp110α, PI3KClassIII, PI3Kp85 and AKT (P=.003, P=.045, P=.050 and P=.028, respectively), between the tumour type (primary vs. recurrence) and cyclin D3 (P=.001), between the tumour size and FGFR3 (P=.035) and between multifocality and cyclin D1 (P=.039). The survival analysis selected FGFR3 (P=.024), PI3Kp110α (P=.014), PI3KClassIII (P=.042) and AKT (P=.008) as markers of early-recurrence-free survival.

Conclusions: There is an increase in protein expression levels in bladder tumour tissue. The overexpression of FGFR3, PI3Kp110α, PI3KClassIII and AKT is associated with increased early-recurrence-free survival for patients with T1 bladder tumours.

Keywords: Bladder cancer; Cáncer de vejiga; Early recurrence; Expresión proteica, Western blot; Protein expression; Recidiva precoz; Western blot.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cyclin D1 / biosynthesis
  • Cyclin D2 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Oncogene Protein v-akt / biosynthesis
  • Phosphatidylinositol 3-Kinases / biosynthesis
  • Prognosis
  • Prospective Studies
  • Receptor, Fibroblast Growth Factor, Type 3 / biosynthesis
  • Survival Analysis
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / mortality*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery

Substances

  • CCND1 protein, human
  • CCND2 protein, human
  • CDKN1A protein, human
  • Cyclin D2
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin D1
  • Phosphatidylinositol 3-Kinases
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3
  • Oncogene Protein v-akt