Macrophage Inhibitory Cytokine-1 (MIC-1) as A Biomarker for Diagnosis 
and Prognosis of Stage I-II Non-small Cell Lung Cancer

Abstract

Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1), member of transforming growth factor-β (TGF-β) superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC). Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001) and benign pulmonary disease patients (P<0.001). A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001), female (P=0.03) and T2 (P=0.022). A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL) was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%). Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035). Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC.

Keywords

• Lung neoplasms
• Macrophage inhibitory cytokine-1
• Tumor biomarker
• Prognosis