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Candidate Biomarkers to Identify Mesothelioma Patients at Risk of Developing Venous Thromboembolism Post-Surgery

ABSTRACT: Pleural Mesothelioma (PM) is an aggressive cancer that attacks thousands of people every year. One of the common treatments is surgery to remove the tumor. Unfortunately, around 11% of patients die from blood clots post-surgery. Current predictive factors such as C-reactive protein, D-Dimer, and abnormal platelet count are not specific. To date, there are no specific blood-based protein biomarkers to identify PM patients at risk of developing Venous Thromboembolism (VTE) post-surgery. In this study, we present a set of host-response plasma protein candidate biomarkers that can predict patients at risk of developing VTE. We employed a quantitative mass spectrometry-based proteomics approach integrated with a multilayered, structured, and systematic evaluation of candidate biomarkers in a cohort of 18 patients, comprising six mesothelioma cases, six mesothelioma controls, and six lung cancer controls. This is the first step towards personalized treatment plans for PM patients undergoing surgery. This study's findings can potentially guide subsequent, larger-scale investigations, highlighting the value of small-scale exploratory research

INSTRUMENT(S): Orbitrap Exploris 240

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: David R Walt

PROVIDER: MSV000100724 | MassIVE | Wed Feb 04 14:17:00 GMT 2026

REPOSITORIES: MassIVE

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Project description:Rationale There is a need for new and better biomarkers for hypertrophic cardiomyopathy (HCM) which correlate more closely with disease progression as determined by clinical imaging and biohumoral information. We have used a combination of heart tissue and plasma proteomics to identify potential biomarkers for HCM and developed them into an exploratory targeted proteomic assay. Objective To identify informative staging biomarkers for HCM and develop them into a blood test. The test using 10 µl of plasma, was developed into a 10 min liquid chromatography-tandem/mass spectrometry (LC-MS/MS) assay to analyze multiple candidate biomarkers and evaluate their association with clinical phenotypes in patients with HCM. Methods and Results Myocardial tissue and plasma samples from patients with HCM and healthy volunteers (controls) were screened using a combined gel- and nano-LC quadrupole time of flight MS approach. Twenty-six potential biomarkers were identified from the proteomics screens and developed into a multiplexed targeted proteomic assay. Their association with clinical phenotypes was tested in plasma samples collected from 207 prospectively recruited participants: 110 patients with HCM (50.1 ± 15.0 years, 70% male; 48 [44%] with identified genetic mutations) and 97 controls (49.6 ± 13.4 years, 58% male), randomly split into training (80 HCM, 67 controls) and validation datasets (30 HCM, 30 controls). Six markers (Aldolase Fructose-Bisphosphate A, Complement C3, Glutathione S-Transferase Omega 1, Ras Suppressor Protein 1, Talin 1, and Thrombospondin 1) were significantly increased (P<0.006) in the plasma of HCM patients compared to controls in the training dataset. These markers correlated with left ventricular (LV) wall thickness, LV mass and % myocardial scar on cardiovascular magnetic resonance imaging. Using supervized machine learning (ML) this panel differentiated HCM from controls (area under the curve: 0.89 in the training dataset, sensitivity 96%, 95% confidence interval [CI] 77–93; specificity 87%, 95%CI 77–94; and 0.87 in the validation dataset, sensitivity 97%, 95%CI 83–100; specificity 77%, 95%CI 58–90). Four of the biomarkers as well as the composite ML score of the plasma proteome correlated with the presence of nonsustained ventricular tachycardia and the estimated 5-year risk of sudden cardiac death. Conclusion By developing a high-throughput, multiplex, and targeted proteomic plasma assay we identified 6 biomarkers that correlate with the presence of disease and with clinical risk score for sudden cardiac death.

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Candidate Biomarkers to Identify Mesothelioma Patients at Risk of Developing Venous Thromboembolism Post-Surgery

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