Evaluation of New Biomarkers in the Prediction of Malignant Mesothelioma in Subjects with Environmental Asbestos Exposure

Our plain-English summary of Evaluation of New Biomarkers in the Prediction of Malignant Mesothelioma in Subjects with Environmental Asbestos Exposure, by M. Demir, H. Kaya, M. Taylan, et al (Lung, 2016).

The study

• Authors: M. Demir, H. Kaya, M. Taylan, A. Ekinci, S. Yılmaz, F. Teke, C. Sezgi, A.C. Tanrikulu, F. Meteroglu, A. Senyigit
• Journal: Lung
• Published: 2016;194(3):409-17
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: The purpose of this study was to investigate the potential value of certain biomarkers in predicting the presence of malignant pleural mesothelioma (MPM) in individuals environmentally exposed to asbestos.

Methods: This prospective study investigated three groups; a control group composed of 41 healthy subjects, an asbestos exposure group consisting of 48 individuals, and a MPM group consisting of 42 patients. Serum levels of soluble mesothelin-related peptide (SMRP), thioredoxin-1 (TRX), epidermal growth factor receptor (EGFR), fibulin-3, syndecan-1 (SDC-1), and mesothelin were determined.

Results: Benign pleural plaques were present in 27 (58.3 %) of the individuals in the asbestos exposure group. The asbestos exposure group had significantly higher mean TRX, SMRP, and mesothelin levels compared to the control group (p = 0.023, p = 0.011, and p < 0.001, respectively). Compared to the asbestos exposure group, the MPM group had significantly higher mean EGFR, TRX, SMRP, and fibulin-3 levels (p = 0.041, p = 0.023, p = 0.002, and p = 0.001, respectively), and significantly lower mean SDC-1 levels (p = 0.002). Unlike the other biomarkers, SMRP and TRX levels increased in a graded fashion among the control, asbestos exposure, and MPM groups, respectively. Area under the curve values for SMRP and TRX were 0.86 and 0.72, respectively (95 % CI 0.79-0.92 and p < 0.001 for SMRP, and 95 % CI 0.62-0.81 and p < 0.001 for TRX). The cut-off value for SMRP was 0.62 nmol/l (sensitivity: 97.6 %, specificity: 68.9 %, positive predictive value (PPV): 56.2 %, and negative predictive value (NPV): 98.3 %) and for TRX was 156.67 ng/ml (sensitivity: 92.9 %, specificity: 77.6 %, PPV: 41.4 %, and NPV: 92.1 %). The combination of the biomarkers reached a sensitivity of 100 %, but had lower specificity (as high as 27.7 %).

Conclusions: Serum biomarkers may be helpful for early diagnosis of MPM in asbestos-exposed cases. SMRP and TRX increased in a graded fashion from the controls to asbestos exposure and MPM groups. These two seem to be the most valuable biomarkers for the diagnosis of MPM, both individually and in combination.

In plain English

This prospective study in Diyarbakir, Turkey (January 2013 to April 2015) measured six blood markers in three groups. The groups were 41 healthy people without asbestos exposure, 48 people who had lived at least 15 years in houses plastered with asbestos-containing soil, and 42 patients with confirmed malignant pleural mesothelioma. The markers were SMRP, thioredoxin-1 (TRX), EGFR, fibulin-3, syndecan-1 and mesothelin. The exposed group had significantly higher TRX, SMRP and mesothelin than the healthy group. Mesothelioma patients had significantly higher EGFR, TRX, SMRP and fibulin-3, and lower syndecan-1, than the exposed group. SMRP and TRX rose step by step across the three groups. SMRP at a 0.62 nmol/l cut-off had sensitivity 97.6% and specificity 68.9%. TRX at 156.67 ng/ml had sensitivity 92.9% and specificity 77.6%. Combinations of two or all three of SMRP, TRX and fibulin-3 reached 100% sensitivity, but specificity was 8.9% to 27.7%. The authors concluded that blood markers may help early diagnosis in exposed people with suspicious clinical and radiologic findings, and that SMRP and TRX seem most valuable. Their stated main limitation was the small number of patients.

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 study comparing serum biomarker levels across three groups (healthy controls, environmentally asbestos-exposed people, and mesothelioma patients), with ROC (diagnostic accuracy) analysis
• Who was studied: 131 people at Dicle University, Diyarbakir, southeastern Turkey, January 2013 to April 2015: 41 healthy controls who lived and worked in an asbestos-free environment, 48 environmentally asbestos-exposed people without radiographic signs of mesothelioma, and 42 patients with histopathologically confirmed malignant pleural mesothelioma. The groups were age- and sex-matched.
• Exposure: Environmental (non-occupational) asbestos exposure from living for at least 15 years in houses plastered with asbestos-containing local soil. The study did not measure fiber type. In the discussion, citing other studies, the authors state that people in southeastern Turkey are mostly exposed to tremolite asbestos fibres. Mean exposure duration was 35.9 ± 11.2 years in the exposure group and 42.9 ± 19.1 years in the mesothelioma group.
• Main results:
  • Pleural plaques were seen on imaging in 27 (reported as 58.3%) of the 48 people in the asbestos exposure group. Biomarker levels were higher in those with plaques than in those without, but these differences were not statistically significant.
  • The asbestos exposure group had significantly higher mean TRX, SMRP and mesothelin levels than the control group (p = 0.023, p = 0.011 and p less than 0.001, respectively).
  • Compared with the asbestos exposure group, the mesothelioma group had significantly higher mean EGFR, TRX, SMRP and fibulin-3 levels (p = 0.041, 0.023, 0.002 and 0.001) and significantly lower mean syndecan-1 levels (p = 0.002).
  • Only SMRP and TRX rose in a graded way from the control group to the asbestos exposure group to the mesothelioma group.
  • Area under the ROC curve was 0.86 for SMRP (95% CI 0.79 to 0.92) and 0.72 for TRX (95% CI 0.62 to 0.81).
  • At a cut-off of 0.62 nmol/l, SMRP had sensitivity 97.6%, specificity 68.9%, PPV 56.2% and NPV 98.3% for mesothelioma.
  • At a cut-off of 156.67 ng/ml, TRX had sensitivity 92.9%, specificity 77.6%, PPV 41.4% and NPV 92.1% for mesothelioma.
  • Combinations of two or all three of SMRP, TRX and fibulin-3 reached 100% sensitivity and NPV, but specificity was low, ranging from 8.9% to 27.7%. The SMRP plus TRX combination had the highest specificity (27.7%, PPV 39.2%), and the triple combination had specificity 8.9% (PPV 33.9%).
• The authors' conclusion: The authors concluded that serum biomarkers may be helpful for early diagnosis of malignant pleural mesothelioma in asbestos-exposed people with suspicious clinical and radiologic findings. In their view, SMRP and TRX seem to be the most valuable markers, both individually and in combination.
• Limitations the authors state:
  • The authors state that the main limitation is the relatively low number of patients.
  • The authors note that the asbestos exposure group was small: the subgroups with and without benign plaques each had fewer than 30 people.

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, Asbestos Exposure, Pleural Mesothelioma, Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), EGFR, Fibulin-3.

Related studies

• Serum biomarkers in patients with mesothelioma and pleural plaques and healthy subjects exposed to naturally occurring asbestos — M. Bayram, I. Dongel, et al. (2014)
• Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals — H.Y. Yang (2019)
• 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)
• HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients — A. Napolitano, D.J. Antoine, et al. (2016)
• Oxidative status and acute phase reactants in patients with environmental asbestos exposure and mesothelioma — C. Sezgi, M. Taylan, et al. (2014)
• Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study — S. Tsim, C. Kelly, et al. (2016)

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