Gene expression profiling on pre- and post-erlotinib tumors from patients with head and neck squamous cell carcinoma

Head Neck. 2013 Jun;35(6):809-18. doi: 10.1002/hed.23036. Epub 2012 Jul 13.

Abstract

Background: The purpose of our work was to identify genomic predictive markers of erlotinib response in patients with head and neck squamous cell carcinoma (HNSCC).

Methods: Tumor tissue biopsies were collected before and after treatment for 39 patients. We analyzed genomic expression of the tumors using microarrays to (1) identify genes differentially expressed in baseline samples in patients who were responders vs nonresponders, (2) characterize erlotinib's effect on gene expression, and (3) identify the pharmacodynamic marker of erlotinib.

Results: Gene expression profiles found no statistically significant differentially expressed genes between responders and nonresponders. An exploratory analysis by combining statistical criteria allowed us to identify genes differentially expressed in nonresponders compared to responders and genes whose expression was modified during erlotinib treatment. Finally, the search of pharmacodynamic markers identified cyclin-dependent kinase 2-interacting protein (CINP) as a potential marker of erlotinib efficacy because its expression decreased only in patients who were responders to the treatment.

Conclusion: This study provides candidate genes potentially involved in erlotinib response in HNSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Biomarkers / analysis
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / surgery
  • Carrier Proteins / genetics
  • Erlotinib Hydrochloride
  • Female
  • Gene Expression Profiling*
  • Glucuronosyltransferase / genetics
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / surgery
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Proteins / genetics
  • Oligonucleotide Array Sequence Analysis
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • CINP protein, human
  • Carrier Proteins
  • NUPR1 protein, human
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • UGT1A1 enzyme
  • Glucuronosyltransferase