CHD1L Expression Increases Tumor Progression and Acts as a Predictive Biomarker for Poor Prognosis in Pancreatic Cancer

Dig Dis Sci. 2017 Sep;62(9):2376-2385. doi: 10.1007/s10620-017-4641-8. Epub 2017 Jun 23.

Abstract

Background: The chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) plays a key role in controlling various cellular phenomena, including immune-mediated inflammation, transformation, apoptosis, cell cycle progression, and proliferation.

Methods: This study investigated the function and clinical significance of CHD1L protein expression in pancreatic cancer (PC). We analyzed CHD1L expression in surgical specimens from 112 PC patients. The correlation between the clinical characteristics and prognosis was also determined. Futhermore, cell proliferation were measured using EDU, and a molecular mechanism of Wnt/β-catenin pathway regulation by CHD1L was explored.

Result: CHD1L protein expression was significantly higher in PC patients with regard to the tumor grade, stage, size, differentiation and lymph node status. Increased CHD1L protein expression was significantly associated with poor overall survival. Multivariate analyses revealed that high CHD1L expression was an independent predictive marker for the recurrence and poor prognosis of pancreatic cancer. Furthermore, silencing of CHD1L expression by RNAi effectively abolished the proliferative abilities of CHD1L in vivo and in vitro. We found that the Wnt/β-catenin pathway contributed to the effect of CHD1L-mediated pancreatic cancer proliferation.

Conclusion: Taken together, our data provide a novel evidence for the biological and clinical significance of CHD1L as a potential biomarker, and we demonstrate that CHD1L-Wnt/β-catenin might be a novel pathway involved in pancreatic cancer progression.

Keywords: CHD1L; Pancreatic cancer; Proliferation; Wnt/β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • DNA Helicases / biosynthesis
  • DNA Helicases / genetics*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Predictive Value of Tests
  • Prognosis
  • Survival Rate / trends

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • DNA Helicases
  • CHD1 protein, human