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.
