8-hydroxy-2--deoxyguanosine and Asbestosis

Workers processing nephrite, antigorite, or talc may be exposed to paragenetic asbestos minerals. An effective screening method for pneumoconiosis in workers exposed to asbestos-contaminated minerals is still lacking. The objective of this study was to assess the diagnostic accuracy of serum and urinary biomarkers for pneumoconiosis in workers exposed to asbestos-contaminated minerals. We conducted a case-control study in a cohort of stone craft workers in Hualien, where asbestos, nephrite, antigorite, and talc are produced. A total of 140 subjects were screened between March 2013 and July 2014. All subjects received a questionnaire survey and a health examination that included a physical examination; chest X-ray; and tests for standard pulmonary function, fractional exhaled nitric oxide, serum soluble mesothelin-related peptide (SMRP), fibulin-3, carcinoembryonic antigen (CEA), and urinary 8-Oxo-2'-deoxyguanosine (8-OHdG)/creatinine. After excluding subjects with uraemia and chronic obstructive pulmonary disease (COPD), we included 48 subjects with pneumoconiosis and 90 control subjects without pneumoconiosis for analysis. In terms of occupational history, 43/48 (90%) case subjects and 68% (61/90) of the control subjects had processed asbestos-contaminated minerals, including nephrite, antigorite, and talc. The case group had decreased pulmonary function in forced vital capacity (FVC), forced expiratory volume in one second, and forced expiratory flow between 25% and 75% of the FVC. The levels of SMRP, fibulin-3, urinary 8-OHdG/creatinine, and CEA were higher in the case group than in the control group. Subjects exposed to nephrite had significantly higher SMRP levels (0.84 ± 0.52 nM) than subjects exposed to other types of minerals (0.60 ± 0.30 nM). A dose-response relationship was observed between the SMRP level and the severity of pneumoconiosis. Machine learning algorithms, including variables of sex, age, SMRP, fibulin-3, CEA, and 8-OHdG/creatinine, can predict pneumoconiosis with high accuracy. The areas under the receiver operating characteristic curves ranged from 0.7 to 1.0. We suggest that SMRP and fibulin-3 could be used as biomarkers of pneumoconiosis in workers exposed to asbestos-contaminated minerals.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Asbestos; Asbestos, Serpentine; Asbestosis; Biomarkers; Carcinoembryonic Antigen; Case-Control Studies; Cohort Studies; Creatinine; Extracellular Matrix Proteins; Female; Forced Expiratory Volume; GPI-Linked Proteins; Humans; Male; Maximal Midexpiratory Flow Rate; Mesothelin; Middle Aged; Minerals; Occupational Exposure; Pneumoconiosis; Taiwan; Talc; Vital Capacity

Improved detection methods for diagnosis of asymptomatic malignant mesothelioma (MM) are essential for an early and reliable detection and treatment of this type of neoplastic disease. Thus, focus has been on finding tumor markers in the blood that can be used for noninvasive detection of MM. Ninety-four asbestos-exposed subjects defined at high risk, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the clinical significance of 8-hydroxy-2'-deoxyguanosine (8OHdG) in WBCs and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors [platelet-derived growth factor beta, hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor beta (VEGFbeta)], and matrix proteases [matrix metalloproteinase (MMP) 2, MMP9, tissue inhibitor of metalloproteinase (TIMP) 1, and TIMP2] for potential early detection of MM. The area under receiver operating characteristic (ROC) curves indicate that 8OHdG levels can discriminate asbestos-exposed subjects from healthy controls but not from MM patients. Significant area under ROC curve values were found for SMRPs, discriminating asbestos-exposed subjects from MM patients but not from healthy controls. Except for platelet-derived growth factor beta, the hepatocyte growth factor, basic fibroblast growth factor, and VEGFbeta can significantly differentiate high-risk individuals from healthy control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, and TIMP2. In addition to the diagnostic performance defined by the ROC analysis, the sensitivity and specificity results of markers with clinical significance were calculated at defined cutoffs. The combination of 8OHdG, VEGFbeta, and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Angiogenesis Inducing Agents; Asbestosis; Biomarkers, Tumor; Case-Control Studies; Deoxyguanosine; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leukocytes; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mesothelioma; Middle Aged; Oligonucleotide Array Sequence Analysis; ROC Curve; Sensitivity and Specificity; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2