Candidate biomarkers to identify mesothelioma patients at risk of developing venous thromboembolism post-surgery

Our plain-English summary of Candidate biomarkers to identify mesothelioma patients at risk of developing venous thromboembolism post-surgery, by A. Shami-Shah, S. Roth, S.R. Morton, et al (Scientific Reports, 2026).

The study

• Authors: A. Shami-Shah, S. Roth, S.R. Morton, B. Budnik, W.G. Richards, R. Bueno, R. Ahmad, D.R. Walt
• Journal: Scientific Reports
• Published: 2026;16(1)
• Read it: PubMed · Publisher · Free full text

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 lack specificity. To date, no blood-based protein biomarkers have been identified to reliably predict 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 could 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.

In plain English

This small exploratory laboratory study searched blood plasma for proteins that might help predict which people with pleural mesothelioma develop venous thromboembolism (blood clots in the veins) after surgery. The authors analyzed stored plasma drawn before surgery in 2010–2011 from 18 patients at Brigham and Women’s Hospital. Six were pleural mesothelioma patients who developed clots after surgery, six were mesothelioma patients who did not, and six were lung cancer patients who did not. Using mass spectrometry, they identified 593 proteins. By overlapping three comparisons between the groups, they selected 33 candidate proteins whose levels differed in the patients who developed clots. Five of these (C4A, CFHR2, CFHR5, F12 and KNG1) belonged to the complement and coagulation pathways. In public cancer data, eight of the 33 genes, including F12 and C4A, varied between mesothelioma stages. The authors concluded that they found several candidate biomarkers that may predict clot risk, and that these need testing in larger groups. They noted the small sample, the lack of correction for multiple statistical testing, and that they did not compare the proteins with the existing D-dimer test.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Small exploratory biomarker discovery study comparing plasma proteins between patient groups using quantitative mass spectrometry proteomics, followed by pathway, cancer-stage (public TCGA data) and literature analyses
• Who was studied: Plasma samples from 18 patients at Brigham and Women’s Hospital, collected before surgery in 2010–2011: six pleural mesothelioma patients who developed VTE after surgery, six pleural mesothelioma patients who did not (controls), and six lung cancer patients who did not develop VTE (controls). The cases were male, aged 65 to 75, with mesothelioma VTE-positive and VTE-negative cases matched on age and histological subtype.
• Exposure: The article does not report asbestos or other fiber exposure. It measured plasma proteins in blood drawn before surgery, comparing patients who did and did not develop venous thromboembolism after surgery.
• Main results:
  • Across all 18 samples, 32,703 peptide-spectrum matches were identified, giving 5694 unique peptides and 593 unique proteins.
  • Mesothelioma patients who developed VTE compared with mesothelioma patients who did not (Group A): 63 proteins up-regulated and 29 down-regulated.
  • Mesothelioma patients who developed VTE compared with lung cancer patients who did not (Group B): 54 proteins up-regulated and 38 down-regulated.
  • Mesothelioma patients without VTE compared with lung cancer patients without VTE (Group C): ten proteins up-regulated and 34 down-regulated.
  • By overlapping the three group comparisons, 33 candidate protein targets (subgroup A′) were selected for further analysis. The table of these 33 lists proteins with both higher and lower levels (fold changes above and below 1).
  • In interaction analysis of the 33 targets, five of the eight proteins in cluster 1 (C4A, CFHR2, CFHR5, F12 and KNG1) were enriched in the complement and coagulation cascades.
  • In public TCGA mesothelioma data, eight of the 33 genes showed fluctuations in expression between cancer stages: PLXNB1, BASP1, VASP, RFC1, F12, VNN1, ALDOC and C4A.
  • Six genes with previously known associations to VTE (CFHR2, CFHR5, KNG1, PKM2, ENPP2 and PF4V1) did not change significantly in expression across mesothelioma cancer stages.
• The authors' conclusion: The authors concluded that they found several biomarkers, which they described as promising, that are associated with VTE and may predict which mesothelioma patients are at risk of blood clots after surgery. They said validation in larger and more diverse cohorts is needed.
• Limitations the authors state:
  • The sample size was small and may not capture the full range of disease variation.
  • The candidate biomarkers were not verified or validated with more specific methods such as ELISA.
  • Because of the small sample size, the primary analyses were not corrected for multiple testing.
  • The STRING interaction analysis includes weaker evidence, so it cannot be concluded definitively that these proteins interact.
  • The candidate biomarkers were not compared with current pre-operative tests such as D-dimer, so the authors cannot conclude they are more specific.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Pleural Mesothelioma, Lung Cancer.

Related studies

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• Commentary: Mesothelioma: The Guinness world record holder in thromboembolism — R.B. Cameron (2020)
• Commentary: Focused attention on proactive identification of deep venous thrombosis after pleurectomy/decortication for malignant pleural mesothelioma — S.S. Groth, R.T. Ripley, et al. (2020)
• A proteomics approach to identify predictive blood biomarkers for pleural mesothelioma in prospective cohorts — E.J. Herman, A. Allione, et al. (2026)
• Risk factors for postoperative acute kidney injury after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: a meta-analysis and systematic review — D. Chen, Y. Ma, et al. (2025)
• Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma — F. Mundt, H.J. Johansson, et al. (2014)

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