High plasmatic IL-8 and low nitrites levels are independent predictors of poor prognosis in nasopharyngeal carcinoma patients


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Ahmed Amine Zergoun1,Taha Merghoub2,Chafia Touil-Boukoffa3,Mehdi Bourouba3
1University of M'hamed Bougara, Boumerdes,2MSKCC,3USTHB

Abstract

Background

Nasopharyngeal carcinoma is a highly invasive inflammatory tumor which lacks predictors of evolution and response to therapy to improve disease management. To this aim, we assessed the systemic production of nitrites and a set of cytokines in association with disease development, and evaluated their relation to patients’ clinical parameters (age, TNM) and prognostic.

 

Method

A cohort of 45 NPC patients was enrolled in this study together with 27 healthy age matched controls. 14 Plasmatic cytokines and nitrites were assessed by multiplexed immunobead-based assay and Griess method. Single biomarker’s variations between controls and untreated patients were assessed by Mann-Whitney test. RFS at 53 months was evaluated using Kaplan-Meier method. A multivariate analysis of the hazard risk ratios was performed using the Cox hazard regression test.

Results

A deregulation in the profile of expression of the plasmatic cytokines was observed among NPC patients. We observed a statistically significant upregulation for IP-10, IL-8, IL-6, IL-12p70 and IL-10. We also observed that IL-12p70, IP-10 and MCP-1 levels were significantly augmented, respectively in men, elderly and with N stage. Multiple correlation analysis revealed presence of a complex profile associating pro-inflammatory, angiogenic and immunomodulatory cytokines in patients compared to controls. The Kaplan-Meier’s survival test revealed that patients with high IL-8 or low nitrites levels were more prone to relapse (log-rank test; p=0.012 and p=0.016, respectively) and that those with both high IL-8 and low nitrites would associate with the worst outcome (p=0.003). The multivariate Cox hazard regression showed that IL-8 (HR= 3.53; 95%CI 1.27-9.81; p=0.016) and nitrites (HR=0.3; 95%CI 0.1-0.86; p=0.026) were independent prognostic factors.

 

Conclusion

Altogether, our results showed NPC development in patients is accompanied with a deregulation of nitrites and cytokines production toward a pro-inflammatory, immunomodulatory and angiogenic profile, and demonstrate that IL-8 and nitrites may serve as independent predictors of poor prognosis.