Serum biomarkers in patients with mesothelioma and pleural plaques and healthy subjects exposed to naturally occurring asbestos

Our plain-English summary of Serum biomarkers in patients with mesothelioma and pleural plaques and healthy subjects exposed to naturally occurring asbestos, by M. Bayram, I. Dongel, A. Akbaş, et al (Lung, 2014).

The study

• Authors: M. Bayram, I. Dongel, A. Akbaş, I. Benli, M.E. Akkoyunlu, N.D. Bakan
• Journal: Lung
• Published: 2014;192(1):197-203
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: This study investigated the diagnostic accuracy of the serum biomarkers osteopontin and mesothelin in discriminating mesothelioma patients from those with other, benign conditions and whether levels of the biomarkers differed in subjects who had inhaled naturally occurring asbestos compared with a non-exposed control group.

Methods: This cross-sectional study studied 24 subjects with mesothelioma, 279 subjects with pleural plaques, 123 "healthy exposed," and 120 control subjects. The Kruskal-Wallis test was performed to compare mesothelin and osteopontin levels of the groups, and receiver operating characteristics curves were generated to determine diagnostic yields of both biomarkers. Multiple linear regression analyses were used to identify associated covariates with osteopontin and mesothelin levels.

Results: Serum osteopontin and mesothelin levels were higher in mesothelioma than in benign asbestos-related diseases and healthy exposed subjects. Both biomarker levels were independently associated with mesothelioma, age and smoking pack years. Mesothelin levels were also associated with body mass index. The sensitivity and specificity of osteopontin in distinguishing mesothelioma from the three other groups were 75 and 86 %, respectively; those of mesothelin were 58 and 83 %, respectively. The sensitivity and specificity to discriminate mesothelioma from pleural plaques and healthy subjects were 93 and 73 %, respectively, if osteopontin and mesothelin levels were higher than their optimal cut off levels.

Conclusions: The combination of serum osteopontin and mesothelin levels can help to distinguish mesothelioma from benign asbestos-related diseases and asbestos-exposed subjects.

In plain English

This cross-sectional study measured two blood markers, osteopontin and mesothelin, in people from Sivas province, Turkey, where some villages lie close to naturally occurring asbestos. It compared four groups: 24 living patients with malignant mesothelioma from the regional cancer registry, 279 villagers with pleural plaques, 123 villagers with normal chest X-rays living within 10 km of rock formations called ophiolites, and 120 control villagers living more than 25 km away. Median levels of both markers were significantly higher in the mesothelioma patients than in each other group. The three other groups had similar levels. At its best cutoff, osteopontin picked up 75% of mesothelioma patients and correctly ruled out 86% of others. For mesothelin the figures were 58% and 83%. Counting a result as positive when either marker was above its cutoff gave 93% and 73%. Higher levels of both markers were also associated with age and smoking pack-years. The authors concluded that the combination can help distinguish mesothelioma from benign asbestos-related disease and from exposed people. They said the markers could not be recommended for screening.

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: Cross-sectional study of serum biomarkers (osteopontin and mesothelin), using ROC curves to assess how well they distinguished mesothelioma from the other groups
• Who was studied: 546 people from Sivas province, Turkey, in four groups. Group 1 was 24 living patients with malignant mesothelioma diagnosed in 2009 and 2010, taken from the Sivas Health Directorate cancer registry. Group 2 was 279 subjects with pleural plaques. Group 3 was 123 'healthy exposed' subjects with normal chest X-rays. Group 4 was 120 control subjects with normal chest X-rays and no environmental exposure. The non-mesothelioma groups came from an earlier field-based study of randomly selected village residents aged 35 or older who had lived in the village for more than 20 years.
• Exposure: Environmental exposure to naturally occurring asbestos. The exposed subjects lived in villages within 10 km of ophiolites. The controls lived in villages more than 25 km from ophiolitic areas. Fiber types and exposure durations were not measured in this study.
• Main results:
  • Median serum osteopontin and mesothelin levels were significantly higher in mesothelioma patients than in subjects with pleural plaques, healthy exposed subjects and control subjects (p less than 0.001 for each).
  • Osteopontin and mesothelin levels were similar in the pleural plaque group, the healthy exposed group and the control group.
  • In distinguishing mesothelioma from all other subjects, the area under the ROC curve was 0.86 for osteopontin and 0.74 for mesothelin.
  • The optimal cutoff for mesothelin was 1.63 nmol/L, giving 58% sensitivity and 83% specificity. The optimal cutoff for osteopontin was 17.273 nmol/L, giving 75% sensitivity and 86% specificity.
  • Counting a result as positive if mesothelin was above 1.63 nmol/L or osteopontin was above 17.273 nmol/L gave 93% sensitivity and 73% specificity for distinguishing mesothelioma from the other conditions.
  • In multiple linear regression across all participants, having mesothelioma, age and smoking pack-years were independently associated with osteopontin levels. The same factors plus body mass index were independently associated with mesothelin levels, with BMI in the negative direction.
  • Mesothelin levels were negatively correlated with body mass index (r = -0.28).
• The authors' conclusion: The authors concluded that the combination of serum osteopontin and mesothelin levels can help to distinguish mesothelioma from benign asbestos-related diseases and from asbestos-exposed subjects. They said use of these biomarkers should be limited to patients with high suspicion of mesothelioma, to support the diagnosis.
• Limitations the authors state:
  • The study lacked precise asbestos exposure durations and information on the histological subtypes and stages of the mesothelioma cases.
  • Findings were not compared with patients who had other cancers.
  • Pleural plaques were diagnosed by chest X-ray, which has low sensitivity. Some subjects may have had plaques visible only on CT.
  • Osteopontin was measured in serum. The authors cite another report that osteopontin is more accurate when measured in plasma.
  • Without prospective longitudinal testing, the authors said the markers could not be recommended for screening, either alone or in combination.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Pleural Plaques, naturally occurring asbestos (NOA), Osteopontin, Mesothelin.

Related studies

• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum — J. Creaney, S. Sneddon, et al. (2013)
• Evaluation of New Biomarkers in the Prediction of Malignant Mesothelioma in Subjects with Environmental Asbestos Exposure — M. Demir, H. Kaya, et al. (2016)
• 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)
• A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma — I. Raiko, H.P. Rihs, et al. (2017)

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