Molecular characteristics of non-small cell lung cancer with reduced CHFR expression in The Cancer Genome Atlas (TCGA) project

Respir Med. 2015 Jan;109(1):131-6. doi: 10.1016/j.rmed.2014.11.004. Epub 2014 Nov 21.

Abstract

Background: CHFR expression has previously been established as a powerful predictor for response to taxane based first-line chemotherapy in non-small cell lung cancer. It is currently unknown however, if reduced CHFR expression correlates with certain molecular subtypes of lung cancer.

Purpose: In order to determine which patients may benefit from CHFR biomarker testing we conducted the present study to characterize clinical and molecular characteristics of patients with reduced vs. high CHFR expression.

Approach: We utilized the extensive molecular and clinical data of the most recent adeno- and squamous cell carcinoma datasets from The Cancer Genome Atlas (TCGA) project. CHFR expression, analyzed by RNA-seq, was classified as high vs. low based on the median CHFR expression level and correlated with the presence or absence of lung cancer specific mutations (EGFR, KRAS, ALK, MET, ERBB2, TP53, STK11, ROS1, RET, NF1, Pik3CA for adenocarcinomas and FGFR1, FGFR2, FGFR3, TP53, STK11, EGFR for squamous cell carcinomas).

Results: Reduced CHFR expression was associated with EGFR exon19/21 mutations in adenocarcinoma OR 0.23 (95%CI: 0.06-0.88) and male gender in squamous cell carcinoma (OR 0.46 (95%CI 0.23-0.92), p = 0.02).

Keywords: CHFR; Lung cancer; Mutations; Personalized medicine; Predictive biomarker; Taxanes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • ErbB Receptors / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genomic Library
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Poly-ADP-Ribose Binding Proteins
  • Sex Factors
  • Ubiquitin-Protein Ligases

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Neoplasm Proteins
  • Poly-ADP-Ribose Binding Proteins
  • CHFR protein, human
  • Ubiquitin-Protein Ligases
  • ErbB Receptors