Loss of DUSP2 predicts a poor prognosis in patients with bladder cancer

Hum Pathol. 2019 Mar:85:152-161. doi: 10.1016/j.humpath.2018.11.007. Epub 2018 Nov 17.

Abstract

Dual-specificity phosphatase 2 (DUSP2), a member of nuclear type I DUSP family, abolishes the activation of mitogen-activated protein kinases (MAPKs) and plays critical roles in the immune processes, inflammatory responses, and cancer progression. Currently, whether DUSP2 is involved in pathogenesis of bladder cancer remains unclear. In this study, we demonstrate that the expression level of DUSP2 was predominantly downregulated in bladder cancer tissues and cell lines as compared with that of paired normal tissues and benign urothelial cells. Besides, the expression of DUSP2 was significantly associated with pathological grade (P = .009), AJCC stage (P = .017), and subtype (P = .001) in The Cancer Genome Atlas cohort and mainly related to TNM stage (P = .016) in the tissue microarray cohort. Kaplan-Meier analysis suggested that patients with low DUSP2 expression had a shorter 5-year overall survival (P = .018 in The Cancer Genome Atlas; P = .012 in tissue microarray) and lower recurrence-free survival (P = .008). Cox regression analysis indicated that reduced DUSP2 was an independent high risk factor for survival prognosis in both cohorts. Taken together, our findings for the first time suggested DUSP2 as a progression and prognosis biomarker for bladder cancer. Whether DUSP2 functions as a tumor suppressor in bladder cancer deserves further studies.

Keywords: Bladder cancer; DUSP2; Expression; Prognosis; Tissue microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Disease Progression
  • Down-Regulation*
  • Dual Specificity Phosphatase 2 / genetics
  • Dual Specificity Phosphatase 2 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Progression-Free Survival
  • Survival Rate
  • Urinary Bladder / metabolism*
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology

Substances

  • DUSP2 protein, human
  • Dual Specificity Phosphatase 2