Personalized biomarkers to monitor disease progression in advanced non-small-cell lung cancer patients treated with icotinib

Clin Chim Acta. 2015 Feb 2:440:44-8. doi: 10.1016/j.cca.2014.11.010. Epub 2014 Nov 15.

Abstract

Background: Disease-specific humoral immune response-related protein complexes in blood are associated with disease progression.

Methods: Thirty-one patients with stage IIIB and IV non-small-cell lung cancer (NSCLC) were administered with oral dose of icotinib hydrochloride (150 mg twice daily or 125 mg 3 times daily) for a 28-continuous-day cycle until diseases progressed or unacceptable toxicity occurred. The levels of immunoinflammation-related protein complexes (IIRPCs) in a series of plasma samples from 31 NSCLC patients treated with icotinib hydrochloride were determined by an optimized native polyacrylamide gel electrophoresis.

Results: Three characteristic patterns of the IIRPCs, named as patterns a, b, and c, respectively, were detected in plasma samples from 31 patients. Prior to the treatment, there were 18 patients in pattern a consisting of 5 IIRPCs, 9 in pattern b consisting of six IIRPCs, and 4 in pattern c without the IIRPCs. The levels of the IIRPCs in 27 patients were quantified. Our results indicate that the time length of humoral immune and inflammation response (TLHIIR) was closely associated with disease progression, and the median TLHIIR was 22.0 weeks, 95% confidence interval: 16.2 to 33.0 weeks, with a lead time of median 11 weeks relative to clinical imaging evidence confirmed by computed tomography or magnetic resonance imaging (the median progression-free survival, 34.0 weeks, 95% confidence interval: 27.9 to 49.0 weeks).

Conclusions: The complex relationships between humoral immune response, acquired resistance, and disease progression existed. Personalized IIRPCs could be indicators to monitor the disease progression.

Keywords: Immunoinflammation-related protein complexes; Non-small-cell lung cancer; Progression-free survival; Time length of disease progression; Time length of humoral immune and inflammatory response.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Biomarkers / blood*
  • Blood Proteins / analysis*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Crown Ethers / adverse effects
  • Crown Ethers / therapeutic use*
  • Disease Progression
  • Drug Monitoring / methods
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Humans
  • Immunity, Humoral / drug effects
  • Inflammation / metabolism
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Precision Medicine / methods
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Time Factors

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Blood Proteins
  • Crown Ethers
  • Quinazolines
  • icotinib