A combined prognostic serum interleukin-8 and interleukin-6 classifier for stage 1 lung cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

Background: The advent of low-dose helical computed tomography for lung cancer screening will likely lead to an increase in the detection of stage I lung cancer. Presently, these patients are primarily treated with surgery alone and approximately 30% will develop recurrence and die. Biomarkers that can identify patients for whom adjuvant chemotherapy would be a benefit could significantly reduce both patient morbidity and mortality. Herein, we sought to build a prognostic inflammatory-based classifier for stage I lung cancer. Methods: We performed a retrospective analysis of 548 European American lung cancer cases prospectively enrolled in the Prostate, Lung, Colorectal and Ovarian study. C-reactive protein, interleukin (IL)-6, IL-8, tumor necrosis factor-α, and IL-1β were measured using an ultrasensitive electrochemiluminescence immunoassay in serum samples collected at the time of study entry. Results: IL-6 and IL-8 were each associated with significantly shorter survival (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.08-1.64; p = 0.007; and HR, 1.3; 95% CI, 1.09-1.67; p = 0.005, respectively). Moreover, a combined classifier of IL-6 and IL-8 were significantly associated with poor outcome in stage I lung cancer patients (HR, 3.39; 95% CI, 1.54-7.48, p = 0.002) and in stage 1 patients with more than or equal to 30 pack-years of smoking (HR, 3.15; 95% CI, 1.54-6.46, p = 0.002). Conclusions: These results further support the association between inflammatory markers and lung cancer outcome and suggest that a combined serum IL-6/IL-8 classifier could be a useful tool for guiding therapeutic decisions in patients with stage I lung cancer.