Background: A blood test for detection of lung cancer (LC) could provide survival benefits in high-risk populations. We conducted a retrospective study as the next step of our effort to develop a test for diagnosis of non-small cell lung carcinoma (NSCLC), the most common form of LC, by measuring levels of protein biomarkers in plasma. Materials and Methods: We quantified levels of 106 proteinaceous biomarkers using multiplexed immunoassays of subjects a) diagnosed with stage I/II NSCLC, b) normal non-smoking controls, and c) normal heavy smoking controls (> 10 p.y.). All groups consisted of Caucasian men and women (93 subjects each, ages range 45-87, Ave 59). The specimens were randomized and tested in a blinded manner. A support vector machine (SVM) algorithm, developed and tested in a pilot study, was used to identify differentially expressed biomarkers in the disease and control groups taking into account patients’ gender. Pathway analysis was applied to characterize pathology- and gender-specific patterns of biomarker expression. Results: In a recent pilot study we developed SVM models that classified subjects to NSCLC or normal using 59 plasma markers or subsets thereof, for both genders combined or separately. When data for both genders were analyzed together, SVM classified subjects to NSCLC or normal and identified 4 differentially expressed markers: EGF, sCD40 ligand, IL-8 and MMP-8; sensitivity (SE) 0.93 (95% CI: 0.88-0.96), specificity (SP) 0.87 (95% CI: 0.80-0.92). Considering the sexes separately, the differentially expressed best subset of markers for men (EGF, IL-8, sFAS, MMP-9 and PAI-1) had both SE and SP of 1.0. For women, the best subset of markers (EGF, sCD40 ligand and IL-8) also yielded SE and SP of 1.0. The present study has further confirmed and refined our earlier findings and expanded panels of diagnostic biomarkers for NSCLC with comparable sensitivities and specificities. Analysis of cellular pathways represented by the discriminatory biomarker signatures suggested a role of sex hormone-driven differences of NSCLC plasma biomarkers. Conclusions: The set of diagnostic biomarkers for NSCLC identified in this study holds significant promise for use in the early diagnosis of lung cancer and warrants validation of findings in other ethnic groups and for potentially confounding diseases in clinical studies.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1733. doi:1538-7445.AM2012-1733