title: Aberrant hypomethylated STAT3 was identified as a biomarker of chronic benzene poisoning through integrating DNA methylation and mRNA expression data.
abstract: Chronic occupational benzene exposure is associated with an increased risk of hematological malignancies such as aplastic anemia and leukemia. The new biomarker and action mechanisms of chronic benzene poisoning are still required to be explored. Aberrant DNA methylation, which may lead to genomic instability and the altered gene expression, is frequently observed in hematological cancers. To gain an insight into the new biomarkers and molecular mechanisms of chronic benzene poisoning, DNA methylation profiles and mRNA expression pattern from the peripheral blood mononuclear cells of four chronic benzene poisoning patients and four health controls that matched age and gender without benzene exposure were performed using the high resolution Infinium 450K methylation array and Gene Chip Human Gene 2.0ST Arrays, respectively. By integrating DNA methylation and mRNA expression data, we identified 3 hypermethylated genes showing concurrent down-regulation (PRKG1, PARD3, EPHA8) and 2 hypomethylated genes showing increased expression (STAT3, IFNGR1). Signal net analysis of differential methylation genes associated with chronic benzene poisoning showed that two key hypomethylated STAT3 and hypermethylated GNAI1 were identified. Further GO analysis and pathway analysis indicated that hypomethylated STAT3 played central roles through regulation of transcription, DNA-dependent, positive regulation of transcription from RNA polymerase II promoter, JAK-STAT cascade and adipocytokine signaling pathway, Acute myeloid leukemia, and JAK-STAT signaling pathway. In conclusion, the aberrant hypomethylated STAT3 might be a potential biomarker of chronic benzene poisoning.
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Bai
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Piye
authors.initials: P
authors.lastname: Niu
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: gaoai0980@163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: gaoai0980@163.com.
authors.forename: Ai
authors.initials: A
authors.lastname: Gao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D054392:Adipokines / Q000235:genetics; D000328:Adult; D001554:Benzene / Q000506:poisoning*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D062965:Cyclic GMP-Dependent Protein Kinase Type I / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D015536:Down-Regulation; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D036143:Receptor, EphA8 / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000096743:Interferon gamma Receptor
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D054392:Adipokines; D001554:Benzene; D015415:Biomarkers; D018797:Cell Cycle Proteins; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D008565:Membrane Proteins; D012333:RNA, Messenger; D036143:Receptor, EphA8; D017471:Receptors, Interferon; D050796:STAT3 Transcription Factor; D000096743:Interferon gamma Receptor; C509689:PARD3 protein, human; C494086:STAT3 protein, human; C569718:PRKG1 protein, human; C584114:GNAI1 protein, human
keywords: Biomarkers; Chronic benzene poisoning; DNA methylation; STAT3