A prospective study of the use of circulating markers as predictors for epidermal growth factor receptor-tyrosine kinase inhibitor treatment in pulmonary adenocarcinoma

Cancer Biomark. 2016;16(1):19-29. doi: 10.3233/CBM-150537.

Abstract

Background: The use of liquid tissue, such as circulating cells, to predict treatment response is attracting more attention.

Objective: The aim of this study was to evaluate association between circulating markers and treatment response.

Methods: One hundred and twelve advanced pulmonary adenocarcinoma patients who were going to receive epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were included. Tumor tissue and plasma specimens were collected before treatment and analyzed for EGFR mutation and plasma IL-6 and IL-8. Pre-treatment peripheral blood CD146+/CD3- cells (as circulating endothelial cells, CECs), CD34+/CD45- cells (as endothelial progenitor cells, EPCs), and CD133+ cells (as cancer stem cells, CSCs) were measured with flow cytometry.

Results: The progression-free survival (PFS) was significantly longer in patients with low CEC, low EPC, and low CSC counts than in those with high cell counts (p < 0.001, 0.041, and 0.001, respectively). Multivariate analysis showed that mutant plasma EGFR (pEGFR) was a poor prognostic factor in EGFR-mutated patients (p = 0.048), and there was a tendency for EGFR mutation-negative patients with high IL-6 level to have worse overall survival (p = 0.051).

Conclusions: CECs, EPCs, CSCs, and mutant pEGFR are useful predictive biomarkers of EGFR-TKI treatment efficacy. IL-6 may predict prognosis in advanced lung cancer.

Keywords: Adenocarcinoma; cancer stem cells; circulating endothelial cells; cytokines; endothelial progenitor cells; epidermal growth factor receptor (EGFR).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers / blood*
  • Cell Count
  • Cytokines / blood
  • DNA Mutational Analysis
  • Endothelial Cells / metabolism
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Immunophenotyping
  • Kaplan-Meier Estimate
  • Lung Neoplasms / blood*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation
  • Neoplastic Stem Cells / metabolism
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Cytokines
  • Protein Kinase Inhibitors
  • ErbB Receptors