title: Increased levels of C-C chemokine RANTES in asbestos exposed workers and in malignant mesothelioma patients from an hyperendemic area.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Maternal and Child Health-IRCCS "Burlo Garofolo"-Trieste, Trieste, Italy; Clinical Unit of Hygiene, Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: Manola
authors.initials: M
authors.lastname: Comar
authors.affiliation: Institute for Maternal and Child Health-IRCCS "Burlo Garofolo"-Trieste, Trieste, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Zanotta
authors.affiliation: Division of Occupational & Preventive Medicine, University Hospital of Pisa, Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bonotti
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Tognon
authors.affiliation: Clinical Unit of Occupational Medicine, Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Negro
authors.affiliation: Division of Occupational & Preventive Medicine, University Hospital of Pisa, Pisa, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cristaudo
authors.affiliation: Clinical Unit of Occupational Medicine, Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bovenzi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001194:Asbestos / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood / Q000235:genetics*; D016207:Cytokines / Q000097:blood / Q000235:genetics; D019353:Endemic Diseases; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D008654:Mesothelioma / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D013539:Simian virus 40 / Q000235:genetics; D014764:Viral Proteins / Q000097:blood / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D016207:Cytokines; D014764:Viral Proteins; D001194:Asbestos