Macrophage Inhibitory Cytokine-1 as a Novel Diagnostic and Prognostic Biomarker in Stage I and II Nonsmall Cell Lung Cancer

Chin Med J (Engl). 2016 Sep 5;129(17):2026-32. doi: 10.4103/0366-6999.189052.

Abstract

Background: Increased level of serum macrophage inhibitory cytokine-1 (MIC-1), a member of transforming growth factor-μ superfamily, was found in patients with epithelial tumors. This study aimed to evaluate whether serum level of MIC-1 can be a candidate diagnostic and prognostic indicator for early-stage nonsmall cell lung cancer (NSCLC).

Methods: A prospective study enrolled 152 patients with Stage I-II NSCLC, who were followed up after surgical resection. Forty-eight patients with benign pulmonary disease (BPD) and 105 healthy controls were also included in the study. Serum MIC-1 levels were measured using an enzyme-linked immunosorbent assay, and the association with clinical and prognostic features was analyzed.

Results: In patients with NSCLC, serum protein levels of MIC-1 were significantly increased compared with healthy controls and BPD patients (all P< 0.001). A threshold of 1000 pg/ml of MIC-1 was found in patients with early-stage (Stage I and II) NSCLC, with sensitivity and specificity of 70.4% and 99.0%, respectively. The serum levels of MIC-1 were associated with age (P = 0.001), gender (P = 0.030), and T stage (P = 0.022). Serum MIC-1 threshold of 1465 pg/ml was found in patients with poor early outcome, with sensitivity and specificity of 72.2% and 66.1%, respectively. The overall 3-year survival rate of NSCLC patients with high serum levels of MIC-1 (≥1465 pg/ml) was lower than that of NSCLC patients with low serum MIC-1 levels (77.6% vs. 94.8%). Multivariate Cox regression survival analysis showed that a high serum level of MIC-1 was an independent risk factor for reduced overall survival (hazard ratio = 3.37, 95% confidential interval: 1.09-10.42, P= 0.035).

Conclusion: The present study suggested that serum MIC-1 may be a potential diagnostic and prognostic biomarker for patients with early-stage NSCLC.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Growth Differentiation Factor 15 / blood*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Survival Rate

Substances

  • GDF15 protein, human
  • Growth Differentiation Factor 15