Is soluble mesothelin-related protein an upfront predictive marker of pleural mesothelioma? A prospective study on Italian workers exposed to asbestos

Our plain-English summary of Is soluble mesothelin-related protein an upfront predictive marker of pleural mesothelioma? A prospective study on Italian workers exposed to asbestos, by R. Filiberti, P. Marroni, F. Spigno, et al (Oncology, 2014).

The study

• Authors: R. Filiberti, P. Marroni, F. Spigno, D.F. Merlo, V. Mortara, P. Caruso, A. Cioè, L. Michelazzi, A. Bruzzone, B. Bobbio, C. Simonassi, L. Del Corso, R. Galli, O. Racchi, G. Dini, R. Linares, M. Mencoboni
• Journal: Oncology
• Published: 2014;86(1):33-43
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Soluble mesothelin-related peptide (SMRP) may be useful in the diagnosis and detection of early stage mesothelioma. We investigated the SMRP upfront predictive role for mesothelioma in asbestos-exposed workers.

Methods: A total of 1,715 subjects underwent a first visit and were invited for a follow-up after 1 and 2 years, with a clinical examination and blood sampling. SMRP was measured by an ELISA assay.

Results: Median SMRP at the first visit was 0.45 [interquartile range (IQR) i.e. 25th-75th percentile: 0.30-0.67 nmol/l]. In all, 1,676 subjects (97.8%) were followed up for a median period of 47.1 months. SMRP was measured at the first visit and at both follow-up visits in 1,536 subjects. At follow-up, 3 subjects were diagnosed with an epithelioid mesothelioma. In these cases, SMRP at the first visit ranged from 0.17 to 0.52 nmol/l. Malignant pleural mesothelioma was diagnosed 9-17 months after the last SMRP evaluation. No SMRP variation was observed during the follow-up. Other 61 miscellaneous cancers were diagnosed (median SMRP at first visit: 0.50 nmol/l, IQR: 0.34-0.71 nmol/l).

Conclusions: Our results did not support the usefulness of SMRP as an early marker for the detection of the disease for a time interval of 1 year.

© 2013 S. Karger AG, Basel.

In plain English

This prospective study in Genova County, Italy, asked whether a blood marker, soluble mesothelin-related peptide (SMRP), could flag malignant pleural mesothelioma early in asbestos-exposed workers. Of 3,080 invited port longshoremen and iron- and steel-mill workers, 1,715 took part. One was found to have mesothelioma at the first visit (SMRP 21.2 nmol/l) and was excluded. Participants were invited to give blood at a first visit and about 1 and 2 years later; 1,536 did so at all three. Median follow-up was 47.1 months. Median SMRP at the first visit was 0.45 nmol/l. During follow-up, 3 subjects were diagnosed with epithelioid pleural mesothelioma. Their first-visit SMRP levels were low (0.52, 0.17 and 0.40 nmol/l); in the two who had later measurements, levels stayed low. Of 61 other cancers diagnosed during follow-up, 4 had first-visit SMRP above the 1.5 nmol/l cut-off. Subjects with asbestos-related pleural lesions had higher levels than healthy subjects. The authors concluded their results did not support SMRP as an early marker for detecting mesothelioma over a 1-year interval. They noted that only 3 cases occurred and participants were relatively young.

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: prospective cohort study with repeated blood SMRP measurements and clinical examinations (first visit, then invitations to follow-up visits about 1 and 2 years later)
• Who was studied: Asbestos-exposed workers in Genova County, Italy, identified from the Italian Agency for Occupational Accident Insurance database: longshoremen in loading/unloading operations and iron- and steel-mill workers who were alive on 1 January 2008, lived in Genova County and had at least 1 year of occupational asbestos exposure. 1,715 of 3,080 invited (55.7%) took part; 1 with mesothelioma at the first visit was excluded, leaving 1,714.
• Exposure: Occupational asbestos exposure (fiber types not specified), on average 29 years (range 1 to 49 years); median estimated cumulative dose 22.4 fibers/cc/years (range 0.10 to 368)
• Main results:
  • Of the workers invited, 1,715 (55.7%) agreed to participate.
  • SMRP was measured at the first visit and at least one follow-up visit in 1,629 subjects (95.0%), and at both follow-up visits in 1,536 subjects (89.6%).
  • Median follow-up was 47.1 months (range 5.0 to 58.6 months).
  • Median SMRP at the first visit was 0.45 nmol/l for the study participants.
  • At the first visit, 40 subjects had SMRP above 1.5 nmol/l, the cut-off the authors used.
  • One subject diagnosed with epithelial pleural mesothelioma at the first visit had SMRP of 21.2 nmol/l and was excluded from the study.
  • During follow-up, 3 subjects were diagnosed with malignant pleural mesothelioma, all epithelioid.
  • In the 3 mesothelioma cases, first-visit SMRP was low (0.52, 0.17 and 0.40 nmol/l), measured 13, 35 and 44 months before diagnosis.
  • The first mesothelioma case (first-visit SMRP 0.52 nmol/l) refused the planned follow-up visit, so there was no later SMRP measurement for this person.
  • In the second mesothelioma case, SMRP was 0.17 nmol/l at the first visit and 0.15 nmol/l at the first follow-up, 17 months before diagnosis.
  • In the third mesothelioma case, SMRP was 0.40, 0.31 and 0.37 nmol/l at the first visit and the two follow-up visits; diagnosis came 9 months after the second follow-up.
  • Median SMRP across all visits showed minor fluctuations, from 0.43 to 0.45 nmol/l.
  • Of 61 other cancers diagnosed during follow-up, 4 had first-visit SMRP above 1.5 nmol/l (1 liver, 1 prostate, 2 bladder). The authors said their data indicate SMRP is not a predictor of cancers other than mesothelioma.
  • At the first visit, median SMRP was 0.43 nmol/l (IQR 0.29 to 0.64) in healthy subjects and 0.65 nmol/l (IQR 0.41 to 1.11) in subjects with asbestos-related pleural lesions (asbestosis, pleural thickening or plaques), p less than 0.001.
  • Among 1,494 subjects without cancer who were successfully followed, 59 (3.9%) had an SMRP value above 1.5 nmol/l.
  • SMRP was associated with age, BMI (inversely), current smoking and estimated asbestos fiber dose; these associations were statistically significant but low.
• The authors' conclusion: The authors concluded, while advising caution, that their results did not support the usefulness of SMRP as an early marker for detecting malignant pleural mesothelioma over a time interval of 1 year.
• Limitations the authors state:
  • Participants were relatively young on average (62.2 years), which could have lowered the chance of finding mesothelioma cases.
  • Only 3 mesothelioma cases were diagnosed, all with low SMRP values.
  • Blood samples from the mesothelioma cases were taken at least 9 months before diagnosis, and there were no SMRP measurements at the time of diagnosis.
  • Kidney function markers (such as blood creatinine) were not collected, so some subjects may have had undetected kidney impairment, which can raise SMRP.

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: Mesothelin, Pleural Mesothelioma, Soluble Mesothelin-Related Peptides (SMRP), Mesothelioma, Epithelioid.

Related studies

• Individual predictors of increased serum mesothelin in asbestos-exposed workers — R. Filiberti, P. Marroni, et al. (2013)
• Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma — L. Santarelli, E. Strafella, et al. (2011)
• Evaluation of soluble mesothelin-related peptide as a diagnostic marker of malignant pleural mesothelioma effusions: its contribution to cytology — P.A. Canessa, M.C. Franceschini, et al. (2013)
• A predictive equation to adjust for clinical variables in soluble mesothelin-related protein (SMRP) levels — E.K. Park, D. Wilson, et al. (2012)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)
• Soluble Mesothelin-Related Peptides to Monitor Recurrence After Resection of Pleural Mesothelioma — B.M. Burt, H.S. Lee, et al. (2017)

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