FP05.02 An Early Detection and Prognostic Blood Biomarkers Signature for Malignant Pleural Mesothelioma Based on Targeted Proteomics

Abstract

We have investigated an academically developed targeted proteomics signature for the early detection and for prognostication of malignant pleural mesothelioma (MPM) from the blood. We have studied a multicenter cohort of more than 400 MPM patients and asbestos exposed donors. Serum samples were processed on 96-well plates for enrichment of N-linked glycoproteins before analysis by liquid-chromatography mass spectrometry (LC-MS) based targeted proteomics for a multiplexed peptide biomarkers signature. We have verified the use of a multiplexed MPM proteomics signature identified in our previous work in cell lines and blood (the original signature was composed of seven peptides, the current signature is a reduced version of six peptides). The multiplexing approach offered by LC-MS proteomics in serum allowed to increase the discriminatory capacity of the signature over the single biomarkers. The proteomics signature presented an AUC of 0.738 and for early stage MPM (stage I/II) AUC was 0.765. This performance was comparable to what we observed using well established and commercially optimized MPM blood biomarkers, underlying the potential of our academic developed strategy once optimized for routine clinical use. The signature presented a negative-likelihood ratio of 0.11 for early stage MPM, highlighting the sensitivity of the approach and its potential utility for MPM early detection strategies, once integrated with complementary MPM biomarkers with high specificity. In addition, the proteomics signature was able to significantly separate high and low risk groups of MPM patients based on their survival (HR of 1.659), supporting in this way treatment decisions based on patients prognosis. The targeted proteomics signature in blood represents an additional diagnostic approach for MPM early detection and treatment decisions.