Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies

Our plain-English summary of Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies, by L. Santarelli, S. Gaetani, F. Monaco, et al (Cancer Epidemiology, Biomarkers & Prevention, 2019).

The study

• Authors: L. Santarelli, S. Gaetani, F. Monaco, M. Bracci, M. Valentino, M. Amati, C. Rubini, A. Sabbatini, E. Pasquini, N. Zanotta, M. Comar, J. Neuzil, M. Tomasetti, M. Bovenzi
• Journal: Cancer Epidemiology, Biomarkers & Prevention
• Published: 2019;28(1):119-126
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Altered miRNA expression is an early event upon exposure to occupational/environmental carcinogens; thus, identification of a novel asbestos-related profile of miRNAs able to distinguish asbestos-induced cancer from cancer with different etiology can be useful for diagnosis. We therefore performed a study to identify miRNAs associated with asbestos-induced malignancies.

Methods: Four groups of patients were included in the study, including patients with asbestos-related (NSCLCAsb) and asbestos-unrelated non-small cell lung cancer (NSCLC) or with malignant pleural mesothelioma (MPM), and disease-free subjects (CTRL). The selected miRNAs were evaluated in asbestos-exposed population.

Results: Four serum miRNAs, that is miR-126, miR-205, miR-222, and miR-520g, were found to be implicated in asbestos-related malignant diseases. Notably, increased expression of miR-126 and miR-222 were found in asbestos-exposed subjects, and both miRNAs are involved in major pathways linked to cancer development. Epigenetic changes and cancer-stroma cross-talk could induce repression of miR-126 to facilitate tumor formation, angiogenesis, and invasion.

Conclusions: This study indicates that miRNAs are potentially involved in asbestos-related malignancies, and their expression outlines mechanism(s) whereby miRNAs may be involved in an asbestos-induced pathogenesis.

Impact: The discovery of a miRNA panel for asbestos-related malignancies would impact on occupational compensation and may be utilized for screening asbestos-exposed populations.

©2018 American Association for Cancer Research.

In plain English

This study looked for blood markers called microRNAs (miRNAs) that might distinguish asbestos-related cancers from other cancers. The authors first screened 384 miRNAs in tumor tissue from 12 patients in Ancona, Italy, who had non-small cell lung cancer (NSCLC) with or without asbestos exposure, or malignant pleural mesothelioma. They then tested the candidates in serum from further patient groups and healthy controls. Four miRNAs (miR-126, miR-205, miR-222 and miR-520g) were stably found in serum. A model using miR-222 and age was built to separate asbestos-related cancers from asbestos-unrelated lung cancer and disease-free people. Its accuracy measure (area under the curve) was 0.706 (0.598-0.814) in training and 0.767 (0.675-0.858) in validation. At the chosen cut-off, 10-15% of asbestos-related cancers were classed as unrelated. Meanwhile, 40-60% of asbestos-unrelated lung cancer and sinonasal cancer patients were classed as asbestos-associated. Among 80 cancer-free asbestos-exposed people, miR-126 and miR-222 were higher only in those currently exposed. The authors concluded that these two miRNAs are likely involved in asbestos-related malignancies. As major limitations, they named the small number of subjects, the difficulty of estimating exposure, and the difficulty of attributing NSCLC to asbestos.

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: Multi-phase biomarker study comparing patient groups and controls: discovery in tumor tissue, then verification, training and validation in serum
• Who was studied: 105 NSCLC patients (60 without and 45 with asbestos exposure), recruited in Ancona, Italy, from January 2011 to March 2017. 74 malignant pleural mesothelioma patients, recruited in Ancona from November 2008 to January 2013. Sinonasal cancer patients from Bologna. 80 cancer-free asbestos-exposed subjects from Trieste. 78 healthy controls who had never been exposed to asbestos.
• Exposure: Occupational and non-occupational (environmental, familial, domestic) asbestos exposure. Jobs included shipbuilders, machine operators, electricians, pipe fitters and construction workers. The cancer-free exposed group had exposure from asbestos cement, rolling stock and shipbuilding, or current exposure during maintenance and remediation of older buildings. A cumulative 'fiber-year' dose was estimated. No fiber types are named.
• Main results:
  • Eleven candidate miRNAs were found in tissue, but only four were stably detected in serum. miR-205 was specific for NSCLC, miR-126 for mesothelioma, and miR-222 and miR-520g were representative of asbestos-related NSCLC.
  • In the training dataset, miR-126 was low in NSCLC and lower still in mesothelioma, compared with controls. All four miRNAs were high in asbestos-related NSCLC.
  • In the training-phase logistic regression for asbestos-related malignancy, the odds ratio for miR-222 was 1.28 (95% CI 1.014-1.616, p=0.038). The odds ratio for age was 1.066 (95% CI 1.018-1.116, p=0.006).
  • The model with miR-222 and age was meant to discriminate asbestos-related malignancies from asbestos-unrelated lung cancer and disease-free subjects. Its AUC was 0.706 (0.598-0.814) in the training dataset and 0.767 (0.675-0.858) in the validation dataset.
  • The cut-off was 0.466 (80% sensitivity, 70% specificity). At this cut-off, 10-15% of asbestos-related malignancies (asbestos-related NSCLC and mesothelioma) were classed as asbestos-unrelated. Meanwhile, 40-60% of asbestos-unrelated NSCLC and sinonasal cancer patients were classed as asbestos-associated.
  • Both miR-126 and miR-222 correlated significantly with the estimated cumulative asbestos fiber dose.
  • To tell NSCLC from controls, a model with miR-205 and miR-222 had an AUC of 0.865 (0.792-0.937).
  • In the cancer-free asbestos-exposed population, miR-126 and miR-222 were high in currently exposed subjects. They were unchanged in formerly exposed subjects, whether or not those subjects had benign asbestos-related diseases.
• The authors' conclusion: The authors concluded that miR-126 and miR-222 are likely involved in asbestos-related malignancies. They also concluded that the pattern of expression points to these miRNAs being involved in asbestos-induced disease processes.
• Limitations the authors state:
  • Small number of enrolled subjects.
  • Difficulty estimating asbestos exposure.
  • Difficulty attributing NSCLC to asbestos as its cause.

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: Etiology, Non-Small Cell Lung Cancer, Pleural Mesothelioma, Angiogenesis, Discovery.

Related studies

• Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy — S. Gaetani, F. Monaco, et al. (2020)
• Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma — L. Santarelli, E. Strafella, et al. (2011)
• Clinical significance of circulating miR-126 quantification in malignant mesothelioma patients — M. Tomasetti, S. Staffolani, et al. (2012)
• Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma — L. Santarelli, S. Staffolani, et al. (2015)
• Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease — T. Cavalleri, L. Angelici, et al. (2017)
• miRNA-503 inhibition exerts anticancer effects and reduces tumor growth in mesothelioma — M. Piccioni, F. Di Meo, et al. (2025)

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