Soluble markers for diagnosis of malignant pleural mesothelioma

Our plain-English summary of Soluble markers for diagnosis of malignant pleural mesothelioma, by A. Cristaudo, A. Bonotti, S. Simonini, et al (Biomarkers in Medicine, 2011).

The study

• Authors: A. Cristaudo, A. Bonotti, S. Simonini, R. Bruno, R. Foddis
• Journal: Biomarkers in Medicine
• Published: 2011;5(2):261-73
• Type of article: Review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive and invasive tumor, whose incidence is expected to peak, in many countries, at the end of the present decade, 20-40 years after the peak of asbestos use (asbestos being the most important etiological factor). MPM has a poor prognosis, in part, owing to a difficult and often late diagnosis hindered by a lack of available tests able to diagnose or predict this cancer in its early stages. Recently, there has been increased interest in noninvasive, economic and well-accepted diagnostic tests for screening of asbestos-exposed subjects, as well as for monitoring response of MPM patients to treatment. Several markers have been studied in biofluids, such as serum, plasma and pleural effusions, especially using ELISA, and some of them are still under investigation. However, only mesothelin and ostepontin have proven levels of sensitivity and specificity that are worth testing in the clinical setting.

In plain English

This article was a review, not a new study. The authors reviewed published medical literature on soluble markers (substances measured in blood serum, plasma or pleural effusion, the fluid around the lung) for diagnosing malignant pleural mesothelioma and monitoring its treatment. They described asbestos exposure as the predominant causal factor for this cancer. The markers reviewed included soluble mesothelin (SMRP), megakaryocyte potentiating factor, osteopontin, CYFRA 21-1, CA 15.3, CA 125, calretinin, CEA, intelectin-1, mammoglobin, tissue polypeptide antigen, VEGF and hyaluronic acid. The review reported three findings from earlier studies on SMRP. High levels were found only in the epithelioid type of mesothelioma. Suggested cut-off values ranged from 0.93 to 2.5 nM. A screening study of previously asbestos-exposed people found a high rate of false-positive results. The authors described osteopontin as lacking adequate specificity. They noted that combining markers had not been shown to beat SMRP alone. The authors concluded that only mesothelin and osteopontin had been suggested as useful in clinical practice, and they called for further studies of known and new markers.

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: Narrative review of published literature
• Who was studied: Published studies measuring soluble markers in serum, plasma or pleural effusion of people with malignant pleural mesothelioma, asbestos-exposed people and other comparison groups
• Exposure: Asbestos exposure, described as the predominant etiological factor; no fiber types are specified. The review assessed soluble markers including mesothelin (SMRP), MPF, osteopontin, CYFRA 21-1, CA 15.3, CA 125, calretinin, CEA, intelectin-1, mammoglobin, TPA, VEGF and hyaluronic acid.
• Main results:
  • In the studies reviewed, high soluble mesothelin levels were found only in epithelioid MPM, not in the sarcomatoid or mixed types
  • There was no single established SMRP cut-off value; different authors suggested values from 0.93 to 2.5 nM for telling MPM patients apart from previously asbestos-exposed people without cancer
  • In a prospective screening study of previously asbestos-exposed people (Park et al.), serum SMRP gave a high rate of false positives
  • In one reviewed study (Pass et al.), a serum osteopontin cut-off of 48.3 ng/ml gave a sensitivity of 77.6% and a specificity of 85.5% for MPM diagnosis
  • In an earlier 2010 study by Cristaudo et al., the best plasma osteopontin cut-off (878.65 ng/ml) gave a sensitivity of 68.8% and a specificity of 84.5%
  • The authors summarized osteopontin as lacking adequate specificity
  • In one reviewed study (Creaney et al. 2007), combining mesothelin and CA 125 did not improve diagnosis over mesothelin alone
  • The authors summarized serum SMRP as seeming to be the most adequate biomarker for MPM diagnosis
• The authors' conclusion: The authors concluded that only mesothelin and osteopontin had been suggested as useful in clinical practice, and that further studies are needed to validate known markers and investigate new ones
• Limitations the authors state:
  • The authors noted that few studies had examined combinations of markers
  • The authors noted that contrasting results between studies could reflect different population sizes and different types of control groups

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Pleural Effusion, Mesothelin.

Related studies

• Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma — L. Santarelli, E. Strafella, et al. (2011)
• Two novel polymorphisms in 5' flanking region of the mesothelin gene are associated with soluble mesothelin-related peptide (SMRP) levels — A. Cristaudo, R. Foddis, et al. (2011)
• A review of transcriptome studies combined with data mining reveals novel potential markers of malignant pleural mesothelioma — O. Melaiu, A. Cristaudo, et al. (2012)
• Soluble mesothelin-related peptides (SMRP) - high stability of a potential tumor marker for mesothelioma — D.G. Weber, D. Taeger, et al. (2007)
• 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)
• Is soluble mesothelin-related protein an upfront predictive marker of pleural mesothelioma? A prospective study on Italian workers exposed to asbestos — R. Filiberti, P. Marroni, et al. (2014)

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