Overexpression of CHD1L is positively associated with metastasis of lung adenocarcinoma and predicts patients poor survival

Oncotarget. 2015 Oct 13;6(31):31181-90. doi: 10.18632/oncotarget.5070.

Abstract

CHD1L (chromodomain helicase/ATPase DNA binding protein 1-like gene) has been demonstrated as an oncogene in hepatocellular carcinoma (HCC), however, the role of CHD1L in non-small-cell lung cancer (NSCLC) tumorigenesis hasn't been elucidated. In this study, the expression and amplification status of CHD1L were examined by immunohistochemistry and fluorescence in situ hybridization respectively in 248 surgically resected NSCLCs. The associations between CHD1L expression and clinicopathologic features and the prognostic value of CHD1L were analyzed. Overexpression and amplification of CHD1L was found in 42.1% and 17.7% of NSCLCs, respectively. The frequency of CHD1L overexpression (53.2% vs. 28.1%, P = 0.002) and amplification (25.2% vs. 8.2%, P = 0.020) in adenocarcinoma (ADC), was much higher than that in squamous cell carcinoma (SCC). CHD1L overexpression was associated closely with ascending pN status (P < 0.001), advanced clinical stage (P = 0.001) and tumor distant metastasis (P = 0.001) in ADCs, but not in SCCs. For the whole cohort and ADC patients, univariate survival analysis demonstrated a significant association of CHD1L overexpression with shortened survival; and in multivariate analysis, CHD1L overexpression was evaluated as a independent predictor for overall survival and distant metastasis free survival. These results suggested that overexpression of CHD1L is positively associated with tumor metastasis of lung ADC, and might serve as a novel prognostic biomarker and potential therapeutic target for lung ADC patients.

Keywords: CHD1L protein; gene amplification; metastasis; non-small-cell lung carcinoma; prognosis.

Publication types

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

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adenocarcinoma / therapy
  • Adenocarcinoma of Lung
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / therapy
  • Chi-Square Distribution
  • DNA Helicases / analysis*
  • DNA Helicases / genetics
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / genetics
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Amplification
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • DNA Helicases
  • CHD1L protein, human