Advanced laboratory medicine using clinical metabonomics for biomarker discovery of Malignant Pleural Effusions (MPE)

Abstract

AIMS OF STUDY: Clinical metabonomics has been widely used in advanced laboratory medicine for the study of disease mechanism and biomarker discovery. Here, we will extend the use of clinical metabonomics to develop new screening test for malignant pleural effusions (MPE). METHODS: 32 malignant and 18 non-malignant PE samples will be analyzed using reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS). Biomarkers for MPE will be determined by metabolome-wide association studies (MWAS) using Receiver Operating Characteristic Curve Explorer and Tester (ROCCET). All markers will be filtered using a metabolome-wide significance level (MWSL) at p-value ≤ 2×10−5. RESULTS: 2731 and 3137 markers were detected in positive and negative ESI spectra respectively. Free fatty acids (FFAs) 16:0, 18:1 and 18:2 were significantly increased in MPE. FFA 18:1 (oleic acid) showed the largest area-under-ROC of 0.96 (95% CI: 0.87–1.00) with sensitivity of 84% and specificity of 100.0% (p-value: 8.23×10−8). DISCUSSION: Pleural fluid oleic acid is a novel biomarker for screening MPE. Using MWAS, the most diagnostic marker can be determined in an unbiased approach. FFAs 16:0, 18:1 and 18:2 are the major products of fatty acid synthase (FASN). The lipogenic phenotype observed in MPE supports an overexpression of FASN in cancer cells which could be a potential therapeutic target.