2024 Hot Topic in Basic & Translational Science: Tolerance & Resistance to Targeted Therapy in NSCLC - Posters-PP01.26: Investigating for Blood Circulating N-Linked Glycoproteins Associated With Immunotherapy Response in Pleural Mesothelioma

PP01.26: Investigating for Blood Circulating N-Linked Glycoproteins Associated With Immunotherapy Response in Pleural Mesothelioma

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This study focuses on exploring blood-circulating N-linked glycoproteins as potential biomarkers predictive of immunotherapy response in pleural mesothelioma (PM). N-glycoproteins are important in cancer development and the immune response. The research employs mass spectrometry (MS) and advanced proteomics techniques, specifically data independent acquisition (DIA-MS), to analyze these glycoproteins in serum or plasma samples, differentiating treatment responders from non-responders.<br /><br />To achieve this, the study established an extensive library of synthetic N-glycopeptides using information from the neXtProt protein database and bioinformatics tools, creating a collection of over 4,400 glycopeptides. This resource covers the majority of human N-glycoproteins documented in neXtProt, allowing for a detailed quantitative investigation of 1,615 specific proteins within blood samples. <br /><br />The DIA-MS workflow successfully detected 680 N-glycoproteins and 1,151 N-glycopeptides in both PM and healthy donor samples, revealing patterns that might inform treatment decisions. The integration of library-based and library-free analyses was found to be complementary, increasing sensitivity and amplifying the detection of lower abundance proteins.<br /><br />The study utilizes neXtProt and WikiPathways databases to interpret proteomic data within biological contexts related to cancer and its pathways. Moreover, targeted proteomics assays have been developed for selected N-glycoproteins to further probe their role in patient cohorts, with specific emphasis on immune checkpoint proteins.<br /><br />In summary, the research combines proteomics data acquisition with robust biological interpretation to identify potential N-glycoproteins circulating in blood that may serve as biomarkers for predicting immunotherapy response in pleural mesothelioma, leveraging both library-based and library-free methods to enhance detection capabilities.

Asset Subtitle

Ferdinando Cerciello

Keywords

N-linked glycoproteins

biomarkers

immunotherapy response

pleural mesothelioma

mass spectrometry

data independent acquisition

synthetic N-glycopeptides

proteomics

immune checkpoint proteins

neXtProt database