A proteomics approach to identify predictive blood biomarkers for pleural mesothelioma in prospective cohorts

Our plain-English summary of A proteomics approach to identify predictive blood biomarkers for pleural mesothelioma in prospective cohorts, by E.J. Herman, A. Allione, C. Viberti, et al (Clinical and Experimental Medicine, 2026).

The study

• Authors: E.J. Herman, A. Allione, C. Viberti, M. Manfredi, A. Russo, K. Sana-Hafeez, N. Kaiser, G. Johnen, T. Brüning, D. Mirabelli, I. Dianzani, A. Agudo, E. Weiderpass, V. Simeon, R. Kaaks, R. Turzanski-Fortner, R. Tumino, L. Milani, J.M. Gálvez-Navas, M.B. Schulze, C. Schiborn, N.C. Castro, G. Masala, M. Guevara, P. Vineis, E. Casalone, G. Matullo
• Journal: Clinical and Experimental Medicine
• Published: 2026;26(1)
• Read it: PubMed · Publisher · Free full text

Abstract

BACKGROUND: Pleural mesothelioma (PM) is a rare, asbestos-linked cancer with a long asymptomatic latency, delaying diagnosis and limiting treatment options. Identifying blood‐based biomarkers that signal disease before symptoms onset could improve surveillance of at‐risk individuals. METHODS: In our work, we conducted a prospective proteomic study of pre-diagnostic serum from 21 PM cases (< 5 years before diagnosis) and 21 asbestos‐exposed controls in the EPIC cohort using SWATH‐MS, followed by ELISA validation. Findings were tested in an independent MoMar cohort of 32 pre‐diagnostic plasma samples (< 1 year before diagnosis) and 32 matched controls. RESULTS: SWATH-MS identified 12 differentially expressed proteins (nominal p < 0.05, fold change > 1.3 or < 0.75). Transferrin and complement C4A were elevated, while beta‐2‐microglobulin and dermcidin were reduced in pre‐diagnostic cases. ELISA confirmed a borderline significant rise in beta‐2‐microglobulin within two years of diagnosis in EPIC. Calretinin and mesothelin were also detected in both cohorts, with the five‐marker panel achieving an AUC of 0.91 (p = 0.001) in MoMar but not reaching significance in EPIC (AUC = 0.88, p = 0.17). CONCLUSIONS: Integrating novel proteomic biomarker candidates with established markers enhances early PM detection in high-risk populations. Larger, multi‐cohort validation is warranted to refine this biomarker panel for clinical surveillance.

In plain English

This study sought blood proteins signaling pleural mesothelioma before diagnosis. In the European EPIC cohort, the authors compared serum from 21 people diagnosed within 5 years of giving blood with 21 controls matched partly on asbestos exposure. Of 323 proteins, the authors reported 12 meeting their selection criteria, though their table lists one at p = 0.054. Transferrin and complement C4 were higher in cases, and beta-2-microglobulin and dermcidin were lower. A second test method confirmed only a borderline significant beta-2-microglobulin difference, in cases sampled 0 to 2 years before diagnosis. In German former asbestos workers (MoMar), three of these proteins showed no statistically significant differences, but calretinin and mesothelin were significantly higher in cases sampled 0 to 2 years before diagnosis. In cases sampled under 2 years before diagnosis, a five-marker panel had an AUC (1.0 is perfect) of 0.91 in MoMar and 0.88 in EPIC. Its gain over beta-2-microglobulin alone was significant only in MoMar. The authors concluded that the combined panel enhances early detection and called for larger studies. They noted MoMar controls had benign asbestos-related disease and kidney function was not measured.

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: Comparison of pre-diagnostic blood samples from people who later developed pleural mesothelioma and matched controls, nested in two prospective cohorts (EPIC for discovery, MoMar for replication). The laboratory analyses were done later on stored samples, using proteomic profiling (SWATH-MS) followed by ELISA.
• Who was studied: EPIC (European multi-center cohort): 21 participants diagnosed with pleural mesothelioma within 5 years of their enrolment blood draw, and 21 controls matched on sex, age, study center and asbestos exposure; 18 men and 3 women in each group. MoMar (26 centers in Germany; former asbestos workers with recognized benign asbestos-related diseases, sampled 2008 to 2018): 32 cases sampled within one year before diagnosis and 32 age- and sex-matched controls with non-cancer asbestos-related conditions. Table 3 lists 43 cases and 43 controls.
• Exposure: Occupational asbestos exposure. In EPIC it was estimated from questionnaire job histories using a job-exposure matrix and grouped as no, low or high exposure. MoMar participants were former asbestos workers. No fiber types were specified for the study participants.
• Main results:
  • EPIC proteomics: of 323 proteins quantified, the authors reported 12 that met their fold-change and nominal p-value (less than 0.05) criteria. However, Table 2 lists one of these 12, MAST2, at p = 0.054.
  • EPIC proteomics: transferrin and complement C4 were higher in pre-diagnostic cases (both FC = 1.4; p = 0.008 and p = 0.009). These were nominal p-values; the false discovery rate was 0.62.
  • EPIC proteomics: beta-2-microglobulin (FC = 0.7, p = 0.035) and dermcidin (FC = 0.6, p = 0.029) were lower in pre-diagnostic cases.
  • EPIC ELISA: beta-2-microglobulin showed a borderline significant decrease in cases sampled 0 to 2 years before diagnosis. Cases sampled 2 to 5 years before diagnosis did not differ significantly from controls (p = 0.26).
  • EPIC ELISA: transferrin, C4 and dermcidin moved in the same direction as in the discovery data but were not statistically significant.
  • MoMar replication: beta-2-microglobulin, transferrin and C4 showed no statistically significant differences between pre-diagnostic cases and asbestos-exposed non-cancer controls.
  • Calretinin was significantly higher in MoMar cases sampled 0 to 2 years before diagnosis (p less than 0.01); the increase in EPIC was not significant. Mesothelin reached significance only in MoMar (p less than 0.0001).
  • MoMar, cases sampled less than 2 years before diagnosis: the five-marker panel (B2M, C4, TF, calretinin, mesothelin) had an AUC of 0.91, significantly better than B2M alone (p = 0.001). In this cohort, B2M alone had an AUC of 0.55 and calretinin plus mesothelin an AUC of 0.84.
  • EPIC, cases sampled less than 2 years before diagnosis: the five-marker panel had an AUC of 0.88, which was not significantly different from B2M alone (p = 0.17). In this cohort, B2M alone had an AUC of 0.71 and calretinin plus mesothelin an AUC of 0.65.
• The authors' conclusion: The authors concluded that combining new proteomic candidates with established markers enhances early detection of pleural mesothelioma in high-risk populations, and that larger multi-cohort validation is warranted.
• Limitations the authors state:
  • MoMar controls had confirmed benign asbestos-related diseases (chronic inflammatory states), whereas EPIC controls were clinically healthy. The authors say this may have narrowed detectable differences.
  • EPIC used serum and MoMar used plasma. The authors note this difference can affect protein stability and ELISA performance.
  • Most MoMar cases were sampled within one year of diagnosis. The authors say this may reduce statistical power and prevents assessing longer-timeframe markers.
  • Kidney function, a major confounder for beta-2-microglobulin, could not be accounted for.
  • MoMar controls had higher baseline calretinin and mesothelin levels than EPIC controls, which reduced discrimination.
  • There is no direct evidence comparing blood calretinin and mesothelin levels between pre-diagnostic lung cancer and pleural mesothelioma.

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, Pleural Mesothelioma, Latency, Calretinin, Mesothelin.

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