Abstract C15: A novel panel of serum biomarkers distinguishes asthma from non‐small cell lung cancer

Abstract

Purpose: Asthma affects an increasing proportion of the population and may predispose sufferers to lung cancer. Frequent misdiagnosis of asthma and lack of early detection tests for lung cancer might be mitigated by better diagnostic tests. We used multiplexed immunoassays and mass spectrometry to identify serum biomarkers capable of distinguishing asthma from non‐small cell lung cancer, the most common type of lung cancer.

Methods: Sera from normal subjects (NO; n = 300), patients with asthma (AST; n=180), and non‐small cell lung cancer (LC; n = 334) were acquired from commercial vendors. Levels of 58 cytokines, chemokines and growth factors were quantified using multiplexed immunoassays. For biomarker discovery, specimens were digested with trypsin and analyzed by liquid chromatography electrospray ionization MS (LC ESI MS/MS). Proteins were identified using Mascot search software. Validation of select biomarkers identified by MS was achieved by immunodetection of target proteins in serum specimens. Data were reduced using inter‐pathology comparisons with statistical significance determined using Student's t‐test.

Results: Multiplexed immunoassays identified 29 analytes with significant (t<0.05) inter‐pathology differences; 14 of these were highly significant (t < 0.0001). We fund a subset of biomarkers with unexpectedly large inter‐gender differences and distinct gender‐specific expression patterns. Serum levels of interleukin‐13 and small inducible cytokine b11 (I‐TAC) showed the greatest difference between AST, LC, and NO sera. MS analysis to date identified 11 differentially expressed proteins that included 3 putative yet unnamed proteins identified by gene sequencing and 1 protein product corresponding to chromosome X open reading frame 38. The presence of select proteins discovered by MS (syntaxin 11, cAMP‐specific 3′,5′‐cyclic phosphodiesterase type 7, and arginase) was confirmed and quantified by immunobloting.

Conclusion: We have identified a group of serum biomarkers having high inter‐pathology discrimination power that are capable of differentiating AST and LC from normal controls and that may potentially be used in diagnostic tests for early detection of lung pathologies. Our experimental strategy is widely applicable to discovery and validation of biomarkers for diverse human diseases, response to a therapy, or pre‐selection of patients for clinical trials.

Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C15.