Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma

Our plain-English summary of Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma, by A. Cristaudo, A. Bonotti, S. Simonini, et al (Journal of Thoracic Oncology, 2011).

The study

• Authors: A. Cristaudo, A. Bonotti, S. Simonini, A. Vivaldi, G. Guglielmi, N. Ambrosino, A. Chella, M. Lucchi, A. Mussi, R. Foddis
• Journal: Journal of Thoracic Oncology
• Published: 2011;6(9):1587-93
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is a lethal tumor related to asbestos exposure. At present, the only instruments for screening and diagnosis are based on radiological tests, posing evident economic and radio-protectionist problems. Some authors are evaluating biological indicators, such as plasma osteopontin (pOPN) and serum soluble mesothelin-related peptides (SMRP). This study aimed to evaluate whether a combination of these two markers could increase sensitivity and specificity in diagnosis of epithelioid MPM.

Methods: We enrolled 93 healthy subjects, 111 individuals with benign respiratory disease (BRD), and 31 patients with MPM, histologically and/or cytologically confirmed. SMRP and pOPN levels were determined using commercially available enzyme-linked immunosorbent assay kits. Though a logistic regression analysis, SMRP and pOPN were combined and translated into a new index, called "combined risk index."

Results: Differences in both SMRP and pOPN mean values between epithelial MPM patients and healthy subjects or BRD patients were statistically significant (p < 0.0001), whereas there was no difference in SMRP and pOPN mean values between healthy subjects and BRD patients. The performance in MPM diagnosis resulted improved by the combination of the two markers. The results of our study should be confirmed by a larger scale and, possibly, a multicenter study, which could better take into consideration the influence of some possible confounding factors such as glomerular filtration rate and other blood parameters.

Conclusions: We combined SMRP and pOPN dosages to increase diagnostic accuracy. This study showed for the first time that combined SMRP and pOPN measurements can increase both sensitivity and specificity in terms of combined risk index.

In plain English

This study from Pisa, Italy, tested whether combining serum soluble mesothelin-related peptides (SMRP) and plasma osteopontin (pOPN) improves diagnosis of epithelioid malignant pleural mesothelioma. Both were measured in 93 healthy subjects and 111 people with benign respiratory disease, all asbestos-exposed workers, plus 31 epithelioid mesothelioma patients. The authors combined the markers into a "combined risk index" using logistic regression. Both markers' mean levels were higher in mesothelioma patients than in other groups. Levels did not differ between healthy subjects and those with benign disease. Comparing healthy subjects with mesothelioma patients, test accuracy (area under the curve) was 0.795 (plus or minus 0.05) for pOPN, 0.762 (plus or minus 0.05) for SMRP and 0.873 (plus or minus 0.043) for both combined. The methods mention 95% confidence intervals, but these margins are not clearly labelled. At 95% specificity, sensitivity was 45.2% for SMRP, 29.5% for pOPN and 64.5% for the combined index. The authors concluded the combination can increase both sensitivity and specificity. They said this needs confirming in a larger, possibly multicenter study, and applies only to the epithelioid type.

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: Diagnostic blood-marker study comparing mesothelioma patients with asbestos-exposed comparison groups. The two markers were combined by logistic regression into a combined risk index, and accuracy was judged with ROC curves.
• Who was studied: Consecutive patients presenting at the University Hospital of Pisa, Italy, in three groups:
• 93 healthy subjects (92 men, 1 woman; mean age 57.2)
• 111 people with benign respiratory disease (BRD), such as lung asbestosis, asbestos pleuritis, emphysema, lung fibrosis or pleural fluid (108 men, 3 women; mean age 60.1). Of these, 13 had pleural plaques.
• 31 patients with epithelioid malignant pleural mesothelioma (24 men, 7 women; mean age 67.4; 19 at stage II, 12 at stage III), enrolled at diagnosis before any treatment.
  Study dates are not given.
• Exposure: The healthy and BRD subjects were all workers previously exposed to asbestos and taking part in a preventive cancer program. Of the 31 mesothelioma patients, 20 (64.5%) had asbestos exposure. Fiber types, products, jobs and doses are not reported. The measured factors were blood levels of SMRP and pOPN.
• Main results:
  • Mean pOPN, given as mean and standard deviation, was:
• 1322.56 (SD 998.98) ng/ml in mesothelioma patients
• 553.10 (SD 387.67) ng/ml in healthy subjects
• 533.77 (SD 394.63) ng/ml in BRD patients
  The difference between mesothelioma patients and each other group was reported as statistically significant.
  • Mean serum mesothelin (SMRP) was:
• 2.52 (SD 4.10) nM in epithelial mesothelioma patients
• 0.71 (SD 0.45) nM in healthy subjects
• 0.82 (SD 0.51) nM in BRD patients
  • Mean SMRP and pOPN levels did not differ between healthy subjects and BRD patients.
  • Comparing healthy subjects with mesothelioma patients, the area under the ROC curve was:
• 0.795 plus or minus 0.05 for pOPN
• 0.762 plus or minus 0.05 for SMRP
• 0.873 plus or minus 0.043 for the combination
  The methods say AUCs were calculated with 95% confidence intervals, but the results do not clearly label what these margins are.
  • From Table 2, at 95% specificity, sensitivity was:
• 45.2% for SMRP
• 29.5% for pOPN
• 64.5% for the combined risk index
  At 80% specificity, sensitivity was 61.3%, 71.0% and 83.9% respectively.
  • At the best cutoff of the combined risk index (0.165), the corresponding SMRP was 1.057 nM and pOPN was 995.04 ng/ml.
  • SMRP and pOPN levels were correlated with each other in healthy controls and BRD patients (Pearson coefficient 0.194, n = 204). They were not correlated in mesothelioma patients or in all study subjects together.
• The authors' conclusion: The authors concluded that combining SMRP and pOPN measurements into a combined risk index can increase both sensitivity and specificity for diagnosing epithelioid mesothelioma. They stated this was shown for the first time.
• Limitations the authors state:
  • The results should be confirmed in a larger, possibly multicenter study. Such a study could better account for possible confounding factors such as glomerular filtration rate and other blood parameters.
  • The findings are limited to the epithelioid type. Mixed and sarcomatoid mesotheliomas were excluded because few cases were available.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Osteopontin, Pleural Mesothelioma, Asbestos Exposure, Soluble Mesothelin-Related Peptides (SMRP), Epithelioid, Confounding.

Related studies

• Comparison between plasma and serum osteopontin levels: usefulness in diagnosis of epithelial malignant pleural mesothelioma — A. Cristaudo, R. Foddis, et al. (2010)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)
• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)
• Changes of mesothelin and osteopontin levels over time in formerly asbestos-exposed power industry workers — M.K. Felten, K. Khatab, et al. (2014)
• Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma — I. Pantazopoulos, P. Boura, et al. (2013)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)

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