Claspin Overexpression Promotes Tumor Progression and Predicts Poor Clinical Outcome in Prostate Cancer

Genet Test Mol Biomarkers. 2021 Feb;25(2):131-139. doi: 10.1089/gtmb.2020.0226.

Abstract

Background: Claspin (CLSPN) expression is acknowledged as a poor clinical prognostic factor in various tumors. However, the clinical characteristics and biological functions of CLSPN in prostate cancer (PCa) are still to be clarified. The aim of our study was to evaluate the association of CLSPN expression during PCa progression and its potential role in prognosis. Methods: We analyzed mRNA expression of the CLSPN gene with various clinicopathological features using the Cancer Genome Atlas and GSE21032 dataset. Immunohistochemical assays were used to detect the protein expression levels of CLSPN in human PCa tissue microarrays. Furthermore, we characterized the role of CLSPN in PCa progression through in vitro experiments using a CLSPN knockout. Results: Immunohistochemistry and public datasets revealed that CLSPN expression was increased in PCa with: a high Gleason score; advanced pathological stage; and positive surgical margins. In addition, upregulation of CLSPN was correlated with shorter biochemical recurrence (BCR)-free survival and overall survival. After we knocked-out CLSPN in DU145 and LNCaP cells, the in vitro phenotypic results showed that the ability of the knockouts to proliferate, migrate, and invade was attenuated; but that apoptosis was promoted. Conclusions: Our data support an oncogenic role for CLSPN in PCa progression. Moreover, increased CLSPN expression was identified as an independent factor in predicting bCR-free survival and disease-free survival in PCa patients.

Keywords: CLSPN; biochemical recurrence-free survival; disease-free survival; progression; prostate cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Aged
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • China / epidemiology
  • Disease Progression
  • Disease-Free Survival
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • CLSPN protein, human