Increased levels of C-C chemokine RANTES in asbestos exposed workers and in malignant mesothelioma patients from an hyperendemic area

Our plain-English summary of Increased levels of C-C chemokine RANTES in asbestos exposed workers and in malignant mesothelioma patients from an hyperendemic area, by M. Comar, N. Zanotta, A. Bonotti, et al (PloS One, 2014).

The study

• Authors: M. Comar, N. Zanotta, A. Bonotti, M. Tognon, C. Negro, A. Cristaudo, M. Bovenzi
• Journal: PloS One
• Published: 2014;9(8):e104848
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Asbestos-induced mesothelial inflammatory processes are thought to be the basic mechanisms underlying Malignant Mesothelioma (MM) development. Detection of MM often occurs at late stage due to the long and unpredictable latent period and the low incidence in asbestos exposed individuals. The aim of this study was to investigate early immunological biomarkers to characterize the prognostic profile of a possible asbestos-induced disease, in subjects from a MM hyperendemic area.

Methods: The Luminex Multiplex Panel Technology was used for the simultaneous measurement of serum levels of a large panel of 47 analytes, including cytokines and growth factors, from workers previously exposed to asbestos (Asb-workers), asbestos-induced MM patients and healthy subjects. In addition, to explore the influence on serum cytokines profile exerted by SV40 infection, a cofactor in MM development, a quantitative real time PCR was performed for sequences detection in the N-terminal and intronic regions of the SV40 Tag gene. Statistical analysis was done by means of the Mann-Whitney test and the Kruskall-Wallis test for variance analysis.

Results: A variety of 25 cytokines linked to pulmonary inflammation and tumor development were found significantly associated with Asb-workers and MM patients compared with healthy controls. A specific pattern of cytokines were found highly expressed in Asb-workers: IFN-alpha (p<0.05), EOTAXIN (p<0.01), RANTES (p<0.001), and in MM patients: IL-12(p40), IL-3, IL-1 alpha, MCP-3, beta-NGF, TNF-beta, RANTES (p<0.001). Notably, the chemokine RANTES measured the highest serum level showing an increased gradient of concentration from healthy subjects to Asb-workers and MM patients (p<0.001), independently of SV40 infection.

Conclusion: This study shows that, in subjects from an hyperendemic area for MM, the C-C chemokine RANTES is associated with the exposure to asbestos fibres. If validated in larger samples, this factor could have the potential to be a critical biomarker for MM prognosis as recently reported for breast tumor.

In plain English

This pilot study measured 47 cytokines and growth factors, which are immune and growth signalling proteins, in blood serum. The subjects came from an Italian area with an unusually high rate of malignant mesothelioma, linked by the authors to past heavy asbestos use in dockyards and shipyards. The authors compared 15 malignant mesothelioma patients, 15 workers previously exposed to asbestos who did not have mesothelioma, and 13 healthy controls. The article did not say which asbestos fiber types were involved. Levels of 26 of the 47 substances differed among the three groups. One chemokine, RANTES, rose step by step across the groups: 0.52 pg/ml in healthy subjects, 23004 pg/ml in exposed workers and 34539 pg/ml in mesothelioma patients. A second laboratory test (ELISA) showed the same pattern. The virus SV40 was found in blood from only 5 mesothelioma patients. RANTES did not differ significantly between patients with and without the virus. The authors concluded that serum RANTES is significantly associated with asbestos exposure. They noted that the study was limited by its small sample size.

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: Pilot study comparing blood serum levels of 47 cytokines and growth factors across three groups (mesothelioma patients, asbestos-exposed workers, healthy controls), with blood testing for SV40 virus
• Who was studied: 43 people: 15 malignant mesothelioma (MM) patients, 15 workers previously exposed to asbestos but free of MM (Asb-workers), and 13 healthy controls, recruited through the University of Trieste, Italy
• Exposure: Asbestos exposure in an Italian area described as a mesothelioma cluster because of past massive asbestos use in dockyards and shipyards; fiber types not stated. SV40 virus infection was also examined.
• Main results:
  • Across the three groups, 26 of the 47 measured substances differed and 21 did not differ significantly
  • RANTES levels rose from healthy subjects (0.52 pg/ml) to Asb-workers (23004 pg/ml) to MM patients (34539 pg/ml), p less than 0.001
  • A confirmatory ELISA test gave RANTES levels of 2390.4 pg/ml in MM patients, 1590.44 pg/ml in Asb-workers and 3.55 pg/ml in healthy subjects, p less than 0.001
  • Compared with healthy controls, Asb-workers had significantly higher levels of 4 cytokines: IFN-alpha (p less than 0.05), Eotaxin (p less than 0.01), IP10 (p less than 0.01) and RANTES (p less than 0.001)
  • Compared with healthy controls, MM patients had significantly higher levels of 7 cytokines: IL-1 alpha, IL-3, IL-12(p40), MCP-3, beta-NGF, TNF-beta and RANTES (p less than 0.001)
  • Compared with Asb-workers, MM patients had higher levels of IL-6 (p less than 0.05), and of CTACK and interferon gamma (p less than 0.01)
  • SV40 was detected in blood from only 5 MM patients
  • Among MM patients, RANTES did not differ significantly between SV40-positive and SV40-negative patients
• The authors' conclusion: The authors concluded that serum levels of the chemokine RANTES are significantly associated with asbestos exposure
• Limitations the authors state:
  • Small sample size

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: Mesothelioma, Biomarker, Cytokine, SV40, Inflammation, Prognosis.

Related studies

• Chemokines involved in the early inflammatory response and in pro-tumoral activity in asbestos-exposed workers from an Italian coastal area with territorial clusters of pleural malignant mesothelioma — M. Comar, N. Zanotta, et al. (2016)
• Asbestos and SV40 in malignant pleural mesothelioma from a hyperendemic area of north-eastern Italy — M. Comar, N. Zanotta, et al. (2012)
• SV40 multiple tissue infection and asbestos exposure in a hyperendemic area for malignant mesothelioma — M. Comar, C. Rizzardi, et al. (2007)
• Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals — C. De Santi, P. Pucci, et al. (2017)
• Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers — I. Bononi, M. Comar, et al. (2016)
• Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2012)

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