Soluble c-Met Levels Correlated With Tissue c-Met Protein Expression in Patients With Advanced Non-Small-Cell Lung Cancer

Clin Lung Cancer. 2017 Jan;18(1):85-91. doi: 10.1016/j.cllc.2016.06.008. Epub 2016 Jun 23.

Abstract

Background: Immunohistochemistry (IHC) and fluorescent in situ hybridization are reliable methods for identifying c-Met protein expression or c-Met gene amplification. However, each technique requires a high-quality tissue sample, which might not be available. The aim of the present study was to investigate the correlation between the soluble c-Met level and tissue c-Met protein expression and the relationship between these markers and patient prognosis.

Materials and methods: In 198 patients with advanced non-small-cell lung cancer, tumor tissue c-Met expression was determined using IHC according to the H score criteria. Positivity was defined as ≥ 50% of cells with strong staining (IHC 3+). The concentration of c-Met protein in paired plasma samples was measured using a human soluble c-Met quantitative enzyme-linked immunosorbent assay kit, and the predictive value was determined using receiver operating characteristic curve analysis.

Results: Of the 198 patients, 140 (70.7%) had tissue c-Met- findings and 58 (29.3%) tissue c-Met+ findings. Receiver operating characteristic curve analysis showed 67.2% specificity and 65.0% sensitivity for predicting tissue c-Met positivity at a plasma c-Met cutoff of 766 ng/mL. The correlation between the soluble c-Met level and tissue c-Met protein expression was significant (Pearson's r = 0.309; P < .001). Patients with high soluble c-Met levels (> 766 ng/mL) had poorer overall survival than patients with low soluble c-Met levels (9.5 vs. 22.2 months; P < .001). Multivariate analyses demonstrated the same result (hazard ratio, 2.15; 95% confidence interval, 1.334-3.446; P = .002).

Conclusion: A significant correlation was found between the plasma soluble c-Met levels and tissue c-Met protein expression in patients with advanced non-small-cell lung cancer. A high level of soluble c-Met was associated with a poor prognosis.

Keywords: Advanced NSCLC; Immunohistochemistry; Prognosis; Soluble c-Met; c-Met.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / blood
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-met / analysis*
  • Proto-Oncogene Proteins c-met / metabolism*
  • Survival Rate
  • Tissue Array Analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MET protein, human
  • Proto-Oncogene Proteins c-met