Prognostic value of the combined expression of tumor-associated trypsin inhibitor (TATI) and p53 in patients with bladder cancer undergoing radical cystectomy

Cancer Biomark. 2019;26(3):281-289. doi: 10.3233/CBM-182143.

Abstract

Background: Urothelial carcinoma of the bladder is a heterogeneous disease for which reliable prognostic molecular biomarkers have not been established.

Objective: To investigate the prognostic value of tumor-associated trypsin inhibitor (TATI) expression combined with p53 expression in bladder cancer patients who have undergone radical cystectomy.

Methods: Tissue microarrays from 110 patients were analyzed immunohistochemically for TATI and p53 protein expression. Complete clinical-pathological information and follow-up data were collected. Univariable Kaplan-Meier analysis and log-rank test were performed to assess the association between TATI and p53 expression patterns with clinical outcomes. Cox's proportional hazard analysis was performed to identify potential independent risk factors for predicting disease progression and evaluate the prognostic value of combining the expression of TATI and p53 on progression-free survival (PFS) and overall survival (OS).

Results: TATI expression was positively correlated with favorable differentiation of bladder cancer, and lower tumor stage. p53 expression was positively related to tumor stage, tumor grade, and lymph-node invasion. Univariate Kaplan-Meier analysis revealed significant differences between TATI-positive vs. TATI-negative and p53-positive vs. p53-negative patients, regarding PFS. Multivariate analysis showed that both TATI and p53 expression were independent factors for predicting disease progression.

Conclusion: TATI expression patterns could enhance the prognostic value of p53 overexpression on progression.

Keywords: Bladder cancer; TATI; combined expression; p53; prognostic value; progression.

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Transitional Cell / mortality*
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / surgery
  • Cystectomy
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Progression-Free Survival
  • Retrospective Studies
  • Survival Rate
  • Tissue Array Analysis
  • Trypsin Inhibitor, Kazal Pancreatic / analysis
  • Trypsin Inhibitor, Kazal Pancreatic / metabolism*
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / metabolism*
  • Urinary Bladder / pathology*
  • Urinary Bladder / surgery
  • Urinary Bladder Neoplasms / mortality*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • SPINK1 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Trypsin Inhibitor, Kazal Pancreatic