Clinical significance of pretreatment plasma biomarkers in advanced non-small cell lung cancer patients

Clin Chim Acta. 2014 Mar 20:430:63-70. doi: 10.1016/j.cca.2013.12.026. Epub 2013 Dec 27.

Abstract

Background: The use of biomarkers for selecting non-small cell lung cancer (NSCLC) patients for treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is essential. The aim of this study was to explore whether biomarkers detected in plasma were predictive for response to EGFR-TKIs and survival time of NSCLC patients.

Methods: Tumor tissues and paired blood were collected from 134 advanced NSCLC patients treated with EGFR-TKIs. EGFR mutations in both types of specimens, and expression of transforming growth factor-alpha and beta one (TGF-α and TGF-β1) were assessed in NSCLC patients. Concentrations of circulating free DNA were detected in plasma from both NSCLC patients and healthy subjects. The clinical significance of EGFR mutations, levels of cytokines, and circulating free DNA was assessed in advanced NSCLC patients.

Results: EGFR mutations were detected in 68 tumor samples and 17 plasma samples of 134 NSCLC patients. The concentrations of circulating free DNA were higher in NSCLC patients than in healthy subjects. Patients with high TGF-β1 level showed shorter overall survival and worse response to EGFR-TKIs than patients with low TGF-β1 level.

Conclusions: Plasma levels of TGF-β1 may be a marker for predicting response to EGFR-TKIs and survival time in NSCLC patients.

Keywords: Biomarker; EGFR; Lung cancer; Plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Disease Progression
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Lung Neoplasms / blood*
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Precision Medicine
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Survival Analysis
  • Transforming Growth Factor alpha / blood
  • Transforming Growth Factor beta1 / blood*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Transforming Growth Factor alpha
  • Transforming Growth Factor beta1
  • EGFR protein, human
  • ErbB Receptors