The Disease-specific Survival From Plasma Il-1 and Il-6 Families Cytokines With Associated Soluble Receptors at Diagnosis in Patients With Head and Neck Squamous Cell Carcinoma Importance of Tnm Stage and Smoking History

Abstract

Abstract The acute-phase cascade (APC) has been correlated with outcome in many different cancers, including head and neck squamous cell carcinoma (HNSCC). A main driver of the APC are the cytokines in the IL-6, IL-1 and TNF cytokine families. We have studied the systemic acute phase soluble cytokine/cytokine receptor profiles in serum (s) for patients with HNSCC. Systemic levels the of Interleukin-6 family cytokines/s-receptors (IL-6, IL-27, IL-31, OSM, CNTF, gp130,IL-6Rα), IL-1 family members (IL-1RA, IL-33Rα/ST2) and TNF-α at diagnosis from 144 HNSCC patients. Five-year disease-specific survival (DSS) was then studied. Increased levels of CRP (p < .001), IL-6 (p < .001), IL-31 (p = .044), IL-1RA (p = .004), IL-6Rα (p = .022) and gp130 (p = .007) were predictors among human papilloma virus (HPV) infection negative (−) patients. Only the IL-6 levels predicted DSS among HPV positive (+) patients. High TNF-α levels showed a trend toward predicting DSS (p = .078) when considering all patients and adjusted for HPV. Adjusting for TNM stage and smoking history, IL-6Rα, gp130, and IL-33Rα/ST2 retained DSS survival prediction. Factor analysis suggests two underlying factors for the present results. The first factor contains the cytokines and the second contains the soluble cytokine receptors. To conclude: High serum levels of IL-6, IL-31 and IL-1RA as well as the soluble receptors IL-6Rα and gp130, and to some extent TNF-α at the time of diagnosis predicted lowered DSS. Clinically, IL-6 levels above 2.5 pg/ml yielded more than 70% specificity and sensitivity for DSS. The cytokine predictions were associated with TNM stage and smoking history, whereas IL-6Rα, gp130 and IL-33Rα/ST2 levels predicted DSS more uniquely.