Increased Levels of C-C Chemokine RANTES in Asbestos Exposed Workers and in Malignant Mesothelioma Patients from an Hyperendemic Area

• Published in: PloS one Vol. 9; no. 8; p. e104848
• Main Authors: Comar, Manola, Zanotta, Nunzia, Bonotti, Alessandra, Tognon, Mauro, Negro, Corrado, Cristaudo, Alfonso, Bovenzi, Massimo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.08.2014; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Analytical chemistry; Antigens; Asbestos; Asbestos - adverse effects; Bioindicators; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Breast cancer; Carbon-carbon composites; Case-Control Studies; Chemokine CCL5 - blood; Chemokine CCL5 - genetics; Chemokines; Childrens health; Concentration gradient; Cytokines; Cytokines - blood; Cytokines - genetics; Disease; Endemic Diseases; Eotaxin; Exposure; Fibers; Gene Expression; Gene Expression Profiling; Growth factors; Health care; Humans; Immunology; Infections; Inflammation; Interferon; Interleukin 1; Interleukin 12; Interleukin 3; Latent period; Lung Neoplasms - blood; Lung Neoplasms - diagnosis; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Maternal & child health; Medical prognosis; Medicine and Health Sciences; Mesothelioma; Mesothelioma - blood; Mesothelioma - diagnosis; Mesothelioma - etiology; Mesothelioma - genetics; Mesothelioma, Malignant; Middle Aged; Nerve growth factor; Occupational exposure; Occupational Exposure - adverse effects; Patients; Preventive medicine; RANTES; Serum levels; Simian virus 40 - genetics; Statistical analysis; Statistical methods; Tumor necrosis factor; Tumor necrosis factor-TNF; Variance analysis; Vascular endothelial growth factor; Viral Proteins - blood; Viral Proteins - genetics; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104848

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. 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. 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. 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.