Increased expression of Capn4 is associated with the malignancy of human glioma

CNS Neurosci Ther. 2014 Jun;20(6):521-7. doi: 10.1111/cns.12248. Epub 2014 Mar 15.

Abstract

Aims: Recent evidence indicates that the increased expression of calpain small subunit 1 (Capn4) is associated with tumorigenesis. This study was designed to explore the role which Capn4 plays in human glioma.

Methods: We detected the expression of Capn4 by immunohistochemistry in tissue microarrays and tissue samples. Following the down-regulation of Capn4 in glioma cell lines by a specific short hairpin RNA, the function of Capn4 in invasion, migration, and proliferation was assessed. We then evaluated the prognostic role of Capn4 using univariate and multivariate analysis in 94 glioblastoma (GBM) patients.

Results: Glioma tissues exhibited notably higher expression of Capn4 compared with control brain tissues and was positively correlated with histological malignancy. The down-regulation of Capn4 in glioma cells led to a decrease in invasion and migration in vitro. Through univariate analysis, the prognosis of GBM patients with Capn4 overexpression was significantly poorer with respect to progression-free survival (PFS) and overall survival (OS). Based on the results of the multivariate analysis, Capn4(high) was demonstrated to be a negative independent prognostic indicator for PFS and OS in GBM patients.

Conclusion: The overexpression of Capn4 is a novel negative prognostic marker, and Capn4 may be used as a new target in therapeutic strategies for human glioma.

Keywords: Capn4; Gliomas; Invasion; Malignancy; Prognosis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Calpain / genetics
  • Calpain / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Female
  • Follow-Up Studies
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Tissue Array Analysis
  • Wound Healing
  • Young Adult

Substances

  • RNA, Small Interfering
  • Calpain
  • CAPNS1 protein, human