Up-regulation of CDHR5 expression promotes malignant phenotype of pancreatic ductal adenocarcinoma

J Cell Mol Med. 2020 Nov;24(21):12726-12735. doi: 10.1111/jcmm.15856. Epub 2020 Oct 6.

Abstract

CDHR5 has been reported to play key roles in carcinogenesis of various cancers, but its roles in pancreatic cancer have not been reported. The present study was designed to investigate its clinical value in pancreatic ductal adenocarcinoma (PDAC). Tissue microarray-based immunohistochemistry was performed to analyse the correlation between CDHR5 expression and clinical and pathological features of PDAC, as well as the CDHR5 expression during tumour progression. Cell function assays were performed to investigate CDHR5's effects on PDAC cells. Moreover, qRT-PCR was applied to investigate the expression of CDHR5 isoforms in PDAC cells. Expression of CDHR5 was higher on the membrane of PDAC cells. This high expression level was associated with shorter overall survival of PDAC patients and was identified as an independent prognostic factor for overall survival by multivariate Cox regression analysis. In addition, expression level of CDHR5 presented an increased trend in the occurrence and progression of PDAC. Cell experiment suggested that CDHR5 could notably promote invasion and migration of PDAC cells. Moreover, analysis of CDHR5 isoforms indicated CDHR5-L was the major isoform expressed in PDAC cell lines. CDHR5 appears to be a promising and novel prognostic factor for PDAC, and its promotion in PDAC metastasis might be ascribed to the isoform CDHR5-L.

Keywords: CDHR5; isoform; pancreatic cancer; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Cadherin Related Proteins
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Phenotype
  • Prognosis
  • Proportional Hazards Models
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Up-Regulation / genetics*

Substances

  • CDHR5 protein, human
  • Cadherin Related Proteins
  • Cadherins
  • Protein Isoforms