A Novel Panel of Serum Biomarkers for MPM Diagnosis

Our plain-English summary of A Novel Panel of Serum Biomarkers for MPM Diagnosis, by A. Bonotti, R. Foddis, S. Landi, et al (Disease Markers, 2017).

The study

• Authors: A. Bonotti, R. Foddis, S. Landi, O. Melaiu, C. De Santi, L. Giusti, E. Donadio, F. Ciregia, M.R. Mazzoni, A. Lucacchini, M. Bovenzi, M. Comar, E. Pantani, A. Pistelli, A. Cristaudo
• Journal: Disease Markers
• Published: 2017;2017:3510984
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy.

In plain English

This Italian study tested whether blood markers could distinguish people with malignant pleural mesothelioma (MPM) from asbestos-exposed people without cancer. The authors tested blood from 43 asbestos-exposed men in a health surveillance program in 2008 to 2013. They also tested samples from 27 MPM patients, all of the epithelioid type, taken at diagnosis before any treatment. Eight markers differed significantly between the two groups. Used alone, IL6 best separated the two groups, with an AUC of 0.880 (95% confidence interval 0.800 to 0.961). A combination of SMRP (mesothelin), osteopontin, IL6 and Vimentin reached an AUC of 0.962 (confidence interval printed as 0.910 to 1000, a misprint, since an AUC cannot exceed 1). At its best cut-off this combination flagged 100% of the MPM patients and correctly cleared 73% of the exposed workers. Adding Desmin and HGF raised that second figure to 85.7%. The authors called the study preliminary, citing the small number of patients and the lack of a separate validation group. They concluded that combining markers could be more useful than single markers for diagnosing MPM, and that further studies are needed.

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: Preliminary diagnostic biomarker study comparing blood levels of markers in MPM patients with those in asbestos-exposed people without cancer, using ROC curve analysis and logistic regression to build marker combinations
• Who was studied: 43 people previously exposed to asbestos and without MPM or another cancer (controls; all male, mean age 58.7) seen at the University Hospital of Pisa, Italy, in 2008 to 2013 within a health surveillance program. Also 27 MPM patients (78% male, mean age 69.4), all histologically confirmed epithelioid type, enrolled at diagnosis before treatment.
• Exposure: Previous asbestos exposure. Fiber types and jobs are not specified. According to Table 1, all controls were asbestos-exposed, with 16.9 ± 8.5 years of exposure. In the MPM group, 63% were asbestos-exposed, with 19.5 ± 10.1 years of exposure among those exposed. The markers measured in blood were SMRP (mesothelin), osteopontin, cytokines and growth factors, Vimentin, Desmin, prelamin A/C, THBS2, TIMP3 and Fibulin 3.
• Main results:
  • SMRP, pOPN, IL6, HGF, Desmin, IP10, Vimentin and THSP2 were statistically different between MPM patients and asbestos-exposed controls.
  • Among single markers, IL6 had the highest AUC: 0.880 (95% CI 0.800 to 0.961).
  • THSP2 was excluded as a diagnostic marker because of its low AUC (0.334).
  • The best three-marker combinations were IL6-pOPN-SMRP (AUC 0.945) and IL6-pOPN-Desmin (AUC 0.950).
  • The best four-marker combination was SMRP, pOPN, IL6 and Vimentin, with an AUC of 0.962. The confidence interval is printed as 0.910 to 1000; the upper limit is a misprint, since an AUC cannot exceed 1.
  • At the best cut-off (0.13), the four-marker combination had a sensitivity of 100% and a specificity of 73%.
  • The six-marker combination (SMRP, pOPN, IL6, Vimentin, Desmin, HGF) reached a sensitivity of 100% and a specificity of 85.7% at the best cut-off.
  • Among MPM patients, marker levels did not differ significantly between women and men, or between asbestos-exposed and non-exposed patients.
• The authors' conclusion: The authors suggested that a combination of multiple markers could be more useful than single markers in diagnosing MPM, and stated that further studies are needed to validate the results.
• Limitations the authors state:
  • Small number of cases analyzed.
  • The very low incidence of the disease reduces the predictive values of biomarkers.
  • The number of patients did not allow separate discovery and independent validation groups.

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: Biomarker, Pleural Mesothelioma, Pleura, Mesothelin, Epithelioid.

Related studies

• Putative Biomarkers for Malignant Pleural Mesothelioma Suggested by Proteomic Analysis of Cell Secretome — S. Lacerenza, F. Ciregia, et al. (2020)
• Improving the cytological diagnosis of high-grade serous carcinoma in ascites with a panel of complementary biomarkers in cell blocks — X. Zhang, L. Chen, et al. (2018)
• Comparison between plasma and serum osteopontin levels: usefulness in diagnosis of epithelial malignant pleural mesothelioma — A. Cristaudo, R. Foddis, et al. (2010)
• A review of transcriptome studies combined with data mining reveals novel potential markers of malignant pleural mesothelioma — O. Melaiu, A. Cristaudo, et al. (2012)
• Exploration of identifying novel serum biomarkers for malignant mesothelioma using iTRAQ combined with 2D-LC-MS/MS — H. Xia, L. Feng, et al. (2021)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)

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