Abstract 3406: The identification of serum cytokine inflammatory markers as classifiers of lung cancer mortality for stage I lung adenocarcinoma: a retrospective cohort study
Authors: Meaney Claire L. , Zingone Adriana , Brown Derek , Yu Yunkai , Cao Liang , Ryan Brid M. 
Published: July 2016

Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide. Low-dose CT (LDCT) imaging is now recommended to screen high-risk lung cancer individuals in the USA. The sensitivity of LDCT has resulted in increased detection of stage I lung cancer and a 20% reduction in lung cancer mortality. The current standard of care for stage 1 lung cancer patients is surgery alone. However, between 20% and 30% of these patients will develop recurrence and therefore are in need of further treatment upon diagnosis.
This study aims to explore and validate biomarkers to identify patients at high-risk of mortality so that additional treatment modalities can be offered at time of diagnosis. Our recent work on a small panel of circulating cytokines identified elevated levels of IL-6, a pro-inflammatory cytokine, as an indicator of poor survival. To further examine the potential of inflammatory biomarkers as prognostic indicators, 125 stage I lung adenocarcinoma cases were selected from the National Cancer Institute-Maryland lung cancer case-control study. This is an on-going prospective study of non-small cell lung cancer based in the greater Baltimore region of the USA.
A panel of 33 inflammatory markers was measured for each case using the Mesoscale V-Plex assay. The magnitude of association between serum inflammatory marker expression levels and lung cancer-specific survival was tested using multivariable Cox proportional hazards regression modeling (Stata 12.0 statistical software). All calculations were adjusted for age, gender, stage and smoking status. Maximum follow up time was 15 years.
Five analytes were significantly associated with shorter survival. In concordance with the previous study, IL-6 was again associated with shorter survival (HR, 2.63; 95% CI, 1.25-5.56). Other cytokines associated with shorter survival included CRP (HR, 2.25; 95% CI, 1.09-4.65), Eotaxin-3 (HR, 2.20; 95% CI, 0.97-4.86), IL-12p40 (HR 1.98; 95% C.I. 1.00 - 3.91), and IL-17 (HR, 2.22; 95% CI, 1.08-4.58). Although IL6 and CRP were positively correlated (Rho = 0.451, P&lt;0.0001), the association between IL-6 and survival was independent of CRP (HR, 2.46; 95% CI, 1.19-5.09).
These results support the potential of cytokine markers as a prognostic tool to further classify stage I lung cancer and thus identify patients in need of additional treatment. The associations identified here justify further investigation of a novel, combined cytokine prognostic classifier to serve as a robust predictor of stage I lung adenocarcinoma survival.
Citation Format: Claire L. Meaney, Adriana Zingone, Derek Brown, Yunkai Yu, Liang Cao, Brid M. Ryan. The identification of serum cytokine inflammatory markers as classifiers of lung cancer mortality for stage I lung adenocarcinoma: a retrospective cohort study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3406.