ENOX2-based early detection (ONCOblot) of asbestos-induced malignant mesothelioma 4-10 years in advance of clinical symptoms

Our plain-English summary of ENOX2-based early detection (ONCOblot) of asbestos-induced malignant mesothelioma 4-10 years in advance of clinical symptoms, by D.J. Morré, B. Hostetler, D.J. Taggart, et al (Clinical Proteomics, 2016).

The study

• Authors: D.J. Morré, B. Hostetler, D.J. Taggart, D.M. Morré, A.W. Musk, B.W. Robinson, J. Creaney
• Journal: Clinical Proteomics
• Published: 2016;13:2
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, caused primarily by exposure to asbestos. In this study, serum presence of mesothelioma-specific protein transcript variants of ecto-nicotinamide adenine dinucleotide oxidase disulfide-thiol exchanger 2 (ENOX2), a recently identified marker of malignancy, were investigated using the ONCOblot tissue of origin cancer detection test.

Methods: Sequential serum samples collected from asbestos-exposed individuals prior to the development of frank mesothelioma were assayed for ENOX2 presence by 2-D gel immunoblot analysis to determine how long in advance of clinical symptoms mesothelioma-specific ENOX2 transcript variants could be detected.

Results: Two mesothelioma-specific ENOX2 protein transcript variants were detected in the serum of asbestos-exposed individuals 4-10 years prior to clinical diagnosis of malignant mesothelioma (average 6.2 years). Either one or both ENOX2 protein transcript variants indicative of malignant mesothelioma were absent in 14 of 15 subjects diagnosed with benign pleural plaques either with or without accompanying asbestosis.

Conclusions: In a population of asbestos-exposed subjects who eventually developed malignant mesothelioma, ENOX2 protein transcript variants characteristic of malignant mesothelioma were present in serum 4-10 years in advance of clinical symptoms. As with all biomarker studies, these observations require validation in a larger, independent cohort of patients and should include prospective as well as retrospective sampling.

In plain English

This study tested whether a blood test called ONCOblot, which looks for cancer-linked forms of a protein called ENOX2, could detect malignant mesothelioma before diagnosis. The authors analyzed stored serum samples from people in a prospective cohort study in Western Australia. The samples came from 17 people with confirmed malignant mesothelioma, all pleural, and from 15 asbestos-exposed people without cancer who had benign pleural plaques, with or without asbestosis. Both mesothelioma-specific ENOX2 forms were found in all 17 mesothelioma patients. Seven of those patients had yearly samples from before their diagnosis. In those seven, both forms appeared 4 to 10 years before clinical symptoms, an average of 6.2 years. Among the 15 people with benign disease, nine had no ENOX2 proteins, five had only one of the two mesothelioma forms, and one had both. The authors called the ENOX2 signals in those six controls false positives and said it was possible, though not proven, that they reflect a pre-malignant stage. The authors concluded that the findings must be confirmed in a larger, independent group 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: Laboratory analysis of stored serum samples comparing mesothelioma patients with asbestos-exposed controls; samples were collected before diagnosis as part of a prospective cohort study
• Who was studied: 17 people with confirmed malignant mesothelioma, all pleural and mostly of epithelial type, mean age at diagnosis 67, confirmed by the Western Australian Mesothelioma Registry. 15 asbestos-exposed controls without malignancy who had benign pleural plaques with or without asbestosis, mean age 72, including two females. Yearly pre-diagnosis samples were available for 7 patients and 3 controls. Collection dates are not given.
• Exposure: Asbestos exposure. This article does not describe fiber type, jobs or doses; the acknowledgments thank the people of the Wittenoom communities.
• Main results:
  • Both mesothelioma-specific ENOX2 forms (Protein 1 and Protein 2) were detected in all 17 mesothelioma patients, in samples taken an average of 7.5 months after diagnosis
  • In the 7 mesothelioma patients with yearly pre-diagnosis samples, both forms were detected 4 to 10 years before clinical symptoms, an average of 6.2 plus or minus 2.6 years; in one patient ENOX2 was detected 10 years before diagnosis
  • Among the 15 asbestos-exposed controls with benign disease, ENOX2 proteins were not detected in 9 (60%)
  • One control (ID 1268) was positive for both mesothelioma-specific forms; the remaining five controls with ENOX2 had only one form (three had only Protein 2 and two had only Protein 1). The authors stated that both forms were required to identify mesothelioma correctly with the ONCOblot test.
  • In patients who developed mesothelioma, ENOX2 spot diameter was 1.95 plus or minus 0.3 mm at first detection, 2.3 plus or minus 0.3 mm at the last date before diagnosis, and 3.2 plus or minus 0.9 mm within the year after diagnosis. The authors described this as roughly a twofold increase in serum ENOX2.
  • In controls followed over time, ENOX2 amounts stayed constant or declined; for control ID 1268, spot diameter declined from 2.0 to 0.8 mm between disease-free years 1 and 10
• The authors' conclusion: The authors concluded that, in asbestos-exposed people who went on to develop malignant mesothelioma, ENOX2 forms characteristic of mesothelioma were present in serum 4 to 10 years before clinical symptoms
• Limitations the authors state:
  • The authors stated that the findings require validation in a larger, independent group of patients, with both prospective and retrospective sampling
  • The authors said longer follow-up would be needed to learn whether a single mesothelioma-type ENOX2 form in benign-disease subjects indicates early changes before mesothelioma
  • The authors described the ENOX2 signals detected in some controls as false positives and said it was possible, but not proven, that they represent a pre-malignant stage

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelioma, Pleural Plaques, Biomarker.

Related studies

• Erratum to: ENOX2-based early detection (ONCOblot) of asbestos-induced malignant mesothelioma 4-10 years in advance of clinical symptoms — D.J. Morré, B. Hostetler, et al. (2016)
• Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma — J. Creaney, N.J. Olsen, et al. (2010)
• Biphasic lung diffusing capacity: detection of early asbestos induced changes in lung function — Z. Dujić, J. Tocilj, et al. (1992)
• Recent advances in the early diagnosis of asbestosis — R. Bégin, G. Ostiguy, et al. (1992)
• A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial — S. Gunatilake, F.J. Brims, et al. (2014)
• Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications — B. Tolani, L.A. Acevedo, et al. (2018)

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