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Proteomics analysis identified serum biomarkers for occupational benzene exposure and chronic benzene poisoning.

ABSTRACT: The study aimed to find novel effect biomarkers for occupational benzene exposure and chronic benzene poisoning (CBP), which might also provide clues to the mechanism of benzene toxicity.We performed a comparative serological proteome analysis between healthy control workers with no benzene exposure, workers with short-term benzene exposure, workers with long-term benzene exposure, and CBP patients using 2D-DIGE and MALDI-TOF-MS. Two of the differentially expressed proteins were then selected to be validated by immune turbidimetric analysis.A total of 10 proteins were found to be significantly altered between different groups. The identified deferentially expressed proteins were classified according to their molecular functions, biological processes, and protein classes. The alteration of 2 important serum proteins among them, apolipoprotein A-I and transthyretin, were further confirmed.Our findings suggest that the identified differential proteins could be used as biomarkers for occupational benzene exposure and CBP, and they may also help elucidate the mechanisms of benzene toxicity.

SUBMITTER: Li P

PROVIDER: S-EPMC6636960 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Proteomics analysis identified serum biomarkers for occupational benzene exposure and chronic benzene poisoning.

Li Peimao P Wu Yuanru Y Zhang Zhimin Z Lin Dafeng D Wang Dianpeng D Huang Xianqing X Zhang Yanfang Y

Medicine 20190601 25

The study aimed to find novel effect biomarkers for occupational benzene exposure and chronic benzene poisoning (CBP), which might also provide clues to the mechanism of benzene toxicity.We performed a comparative serological proteome analysis between healthy control workers with no benzene exposure, workers with short-term benzene exposure, workers with long-term benzene exposure, and CBP patients using 2D-DIGE and MALDI-TOF-MS. Two of the differentially expressed proteins were then selected to ...[more]

PMID: 31232959

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Project description:Epigenetic aging biomarkers are associated with increased morbidity and mortality. We evaluated if occupational exposure to three established chemical carcinogens is associated with acceleration of epigenetic aging. We studied workers in China occupationally exposed to benzene, trichloroethylene (TCE) or formaldehyde by measuring personal air exposures prior to blood collection. Unexposed controls matched by age and sex were selected from nearby factories. We measured leukocyte DNA methylation (DNAm) in peripheral white blood cells using the Infinium HumanMethylation450 BeadChip to calculate five epigenetic aging clocks and DNAmTL, a biomarker associated with leukocyte telomere length and cell replication. We tested associations between exposure intensity and epigenetic age acceleration (EAA), defined as the residuals of regressing the DNAm aging biomarker on chronological age, matching factors and potential confounders. Median differences in EAA between exposure groups were tested using a permutation test with exact p-values. Epigenetic clocks were strongly correlated with age (Spearman r > 0.8) in all three occupational studies. There was a positive exposure-response relationship between benzene and the Skin-Blood Clock EAA biomarker: median EAA was -0.91 years in controls (n = 44), 0.78 years in workers exposed to <10 ppm (n = 41; mean benzene = 1.35 ppm; p = 0.034 vs. controls), and 2.10 years in workers exposed to ≥10 ppm (n = 9; mean benzene = 27.3 ppm; p = 0.019 vs. controls; ptrend = 0.0021). In the TCE study, control workers had a median Skin-Blood Clock EAA of -0.54 years (n = 71) compared to 1.63 years among workers exposed to <10 ppm of TCE (n = 27; mean TCE = 4.22 ppm; p = 0.035). We observed no evidence of EAA associations with formaldehyde exposure (39 controls, 31 exposed). Occupational benzene and TCE exposure were associated with increased epigenetic age acceleration measured by the Skin-Blood Clock. For TCE, there was some evidence of epigenetic age acceleration for lower exposures compared to controls. Our results suggest that some chemical carcinogens may accelerate epigenetic aging.

Project description:BackgroundThe genotoxicity of benzene has been investigated in dozens of biomonitoring studies, mainly by studying (classical) chromosomal aberrations (CAs) or micronuclei (MN) as markers of DNA damage. Both have been shown to be predictive of future cancer risk in cohort studies and could, therefore, potentially be used for risk assessment of genotoxicity-mediated cancers.ObjectivesWe sought to estimate an exposure-response curve (ERC) and quantify between-study heterogeneity using all available quantitative evidence on the cytogenetic effects of benzene exposure on CAs and MN respectively.MethodsWe carried out a systematic literature review and summarized all available data of sufficient quality using meta-analyses. We assessed the heterogeneity in slope estimates between studies and conducted additional sensitivity analyses to assess how various study characteristics impacted the estimated ERC.ResultsSixteen CA (1,356 individuals) and 13 MN studies (2,097 individuals) were found to be eligible for inclusion in a meta-analysis. Studies where benzene was the primary genotoxic exposure and that had adequate assessment of both exposure and outcomes were used for the primary analysis. Estimated slope estimates were an increase of 0.27% CA [(95% CI: 0.08%, 0.47%); based on the results from 4 studies] and 0.27% MN [(95% CI: -0.23%, 0.76%); based on the results from 7 studies] per parts-per-million benzene exposure. We observed considerable between-study heterogeneity for both end points (I2>90%).DiscussionOur study provides a systematic, transparent, and quantitative summary of the literature describing the strong association between benzene exposure and accepted markers of genotoxicity in humans. The derived consensus slope can be used as a best estimate of the quantitative relationship between real-life benzene exposure and genetic damage in future risk assessment. We also quantitate the large between-study heterogeneity that exists in this literature, a factor which is crucial for the interpretation of single-study or consensus slopes. https://doi.org/10.1289/EHP6404.

Project description:PurposeScleritis is an extremely painful and potentially blinding inflammation of the sclera with unknown pathogenesis and unpredictable course. To gain insight in its disease process and identify biomarker candidates, we performed extensive proteomics in serum and tear fluid.DesignProspective multicenter cohort study.ParticipantsA total of 121 patients with noninfectious scleritis (of which 39 active cases), 30 healthy controls, and 23 disease controls (uveitis and rheumatoid arthritis) were enrolled in the Netherlands from 2020 to 2022.MethodsSerum, tear fluid of both eyes, and clinical data were gathered. The level of 368 inflammatory proteins was measured using proximity extension assays. Results were validated in an independent cohort of 15 patients with scleritis, and using addressable laser bead immunoassay, or enzyme-linked immunoassays. In addition, we studied an extended panel of matrix metalloproteinases in tear fluid of necrotizing scleritis with addressable laser bead immunoassay.Main outcome measuresStatistically significant differences in the level of inflammatory proteins between patients with scleritis and control groups.ResultsProteomics revealed 18 significantly upregulated or downregulated serum proteins in active scleritis cases compared with all control groups in both the discovery cohort and the validation cohort. The most upregulated protein was nuclear migration protein nudC (NudC; P = 0.0032), a protein involved in neurogenesis. The other significant hits included proteins involved in T-cell activation, apoptosis, epithelial barrier maintenance, and angiogenesis. Our tear fluid analysis showed matrix metalloproteinase 9 (MMP9) to be upregulated in the tear fluid of patients with scleral necrosis.ConclusionsThe results of our proteomics analysis suggest a role for neurogenesis, T-cell activation, disruption of epithelial barrier, and angiogenesis in the pathogenesis of scleritis, and highlight MMP9 and NudC as biomarkers with potential clinical relevance.Funding disclosuresThe authors have no proprietary or commercial interest in any materials discussed in this article.

Project description:Serum components of sepsis patients vary with the severity of infection, the resulting inflammatory response, per individual, and even over time. Tracking these changes is crucial in properly treating sepsis. Hence, several blood-derived biomarkers have been studied for their potential in assessing sepsis severity. However, the classical approach of selecting individual biomarkers is problematic in terms of accuracy and efficiency. We therefore present a novel approach for detecting biomarkers using longitudinal proteomics data. This does not require a predetermined set of proteins and can therefore reveal previously unknown related proteins. Our approach involves examining changes over time of both protein abundance and post-translational modifications in serum, using two-dimensional gel electrophoresis (2D-PAGE). 2D-PAGE was conducted using serum from n = 20 patients, collected at five time points, starting from the onset of sepsis. Changes in protein spots were examined using 49 spots for which the signal intensity changed by at least two-fold over time. These were then screened for significant spikes or dips in intensity that occurred exclusively in patients with adverse outcome. Individual level variation was handled by a mixed effects model. Finally, for each time transition, partial correlations between spots were estimated through a Gaussian graphical model (GGM) based on the ridge penalty. Identifications of spots of interest by tandem mass spectrometry revealed that many were either known biomarkers for inflammation (complement components), or had previously been suggested as biomarkers for kidney failure (haptoglobin) or liver failure (ceruloplasmin). The latter two are common complications in severe sepsis. In the GGM, many of the tightly connected spots shared known biological functions or even belonged to the same protein; including hemoglobin chains and acute phase proteins. Altogether, these results suggest that our screening method can successfully identify biomarkers for disease states and cluster biologically related proteins using longitudinal proteomics data derived from 2D-PAGE.

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Proteomics analysis identified serum biomarkers for occupational benzene exposure and chronic benzene poisoning.

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Proteomics analysis identified serum biomarkers for occupational benzene exposure and chronic benzene poisoning.

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