Prognostic Significance Of Plasma IL-35 Levels In NSCLC Patients

Background:Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all lung cancer cases. The prognosis of NSCLC is dismal due to lack of efficient biomarkers. Interleukin-35(IL-35) is a novel member of IL-12 family. IL-35 is a heterodimer cytokine comprised of the subunit Epstein-Barr virus-induced gene 3 (EBI3) and the p35 subunit of IL-12. Recent studies have demonstrated that IL-35 exerted immunological functions in autoimmune diseases, infections and cancer. However, the expression and clinical significance of IL-35 in NSCLC were unclear.Methods:Plasma from 106 NSCLC patients and 78 healthy controls was subjected to IL-35 enzyme-linked immunosorbent assay (ELISA) test and relationships between plasma IL-35 levels and clinical characteristics were evaluated. The correlation of IL-35 and overall survival was analyzed using Kaplan-Meier method. The prognostic value of IL-35 was tested using univariate and multivariate analysis.Results:Circulating IL-35 levels were significantly higher in the NSCLC group in comparison with the HC group (21.37±11.55 pg/ml vs.10.09±5.32 pg/ml,p<0.001). Correlation analysis by subgroup indicated that plasma IL-35 correlated positively with tumor TNM stage (p<0.001) andlymph node metastases (p<0.0001). Using a cutoff level of 20.26 pg/ml (median value), IL-35 showed an inverse correlation with overall survival. Univariate and multivariate analysis indicated that plasma IL-35 was an independent prognostic factor for NSCLC patients.Conclusion:Circulating IL-35 in NSCLC patients significantly increased. IL-35 is a promisingpotential biomarker in prognostication of clinical outcome of NSCLC patients and the regulation of IL-35 expression may provide a new target for the treatment of NSCLC patients.