Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases

Our plain-English summary of Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases, by S. Ying, Z. Jiang, X. He, et al (Disease Markers, 2017).

The study

• Authors: S. Ying, Z. Jiang, X. He, M. Yu, R. Chen, J. Chen, G. Ru, Y. Chen, W. Chen, L. Zhu, T. Li, Y. Zhang, X. Guo, X. Yin, X. Zhang, J. Lou
• Journal: Disease Markers
• Published: 2017;2017:5756102
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine and is one of the most intriguing molecules in inflammatory disorders and cancers. Notably, HMGB1 is a potential therapeutic target and novel biomarker in related diseases. However, the diagnostic value of HMGB1 for benign and malignant asbestos-related diseases (ARDs) remains unclear. In this work, we detected preoperative serum HMGB1 levels in Chinese asbestos-exposed (AE) and ARDs populations and further evaluated the diagnostic value of HMGB1 in patients with certain types of ARDs, including those with pleural plaques, asbestosis, or malignant mesothelioma (MM). The experimental data presented that the serum level of HMGB1 was significantly elevated in AE and ARDs subjects. Our findings indicated that serum HMGB1 is a sensitive and specific biomarker for discriminating asbestosis- and MM-affected individuals from healthy or AE individuals. In addition, serum matrix metalloproteinases 2 and 9 are not correlated with HMGB1 in ARDs. Thus, our study provides supporting evidence for HMGB1 as a potential biomarker either for the clinical diagnosis of high-risk AE cohorts or for evaluating ARDs.

In plain English

The authors measured HMGB1, an inflammation-related blood protein, in 497 people from towns in Southeast China with a long history of asbestos industry. The groups were 71 healthy unexposed controls, 170 people exposed at work for under 10 years and 129 for 10 years or more (all with normal chest X-rays), 81 with pleural plaques, 31 with asbestosis and 15 with malignant pleural mesothelioma. Median HMGB1 was 41.68 ng/mL in controls and significantly higher in every other group: 50.06 ng/mL and 50.42 ng/mL in the two exposed groups, 49.77 ng/mL with pleural plaques, 58.77 ng/mL in asbestosis and 60.23 ng/mL in mesothelioma. The asbestosis and mesothelioma groups were significantly higher than the control, exposed and plaque groups, but did not differ from each other. In separating mesothelioma patients from healthy controls, a cut-off of 52.16 ng/mL gave 100% sensitivity and 80.28% specificity. HMGB1 could not separate mesothelioma from asbestosis, which the authors said limits its clinical use. The authors concluded that serum HMGB1 is a sensitive and specific biomarker for distinguishing asbestosis and mesothelioma from healthy or asbestos-exposed individuals.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Clinical biomarker study comparing blood (serum) levels of HMGB1, MMP2 and MMP9 across groups of unexposed, asbestos-exposed and asbestos-disease subjects, with diagnostic accuracy (ROC curve) analysis
• Who was studied: 497 subjects from several small neighboring towns in Southeast China with a long history of asbestos industry (the article gives the years 1960 to 2012). They were split into six groups: 71 healthy controls with no known asbestos exposure and normal chest X-rays; 170 occupationally exposed for less than 10 years with normal chest X-rays; 129 occupationally exposed for over 10 years with normal chest X-rays; 81 with pleural plaques; 31 with asbestosis; and 15 with malignant pleural mesothelioma.
• Exposure: Occupational asbestos exposure, largely in asbestos textile work. Exposure duration was the years worked in asbestos jobs. Potential exposure (mg/m3 × years) was estimated from total dust measurements taken from 1984 to 2010, with median dust concentrations of 0.7 mg/m3 in small household textile workshops and 5.9 mg/m3 in a large textile manufactory. Median potential exposure levels were 17.7 (under 10 years exposed), 70.8 (10 years or more), 50.2 (pleural plaques), 11.9 (asbestosis) and 11.0 (mesothelioma) mg/m3-years. In the discussion, the authors state that chrysotile was the main raw material for asbestos product manufacturers in the region studied.
• Main results:
  • Median serum HMGB1 was 41.68 ng/mL in healthy controls. It was significantly higher in both exposed groups: 50.06 ng/mL in those exposed under 10 years and 50.42 ng/mL in those exposed 10 years or more. The two exposed groups did not differ significantly from each other.
  • Pleural plaque group: median HMGB1 49.77 ng/mL, significantly higher than controls and roughly equal to the two exposed groups.
  • Asbestosis group: median HMGB1 58.77 ng/mL, significantly higher than the control, both exposed, and pleural plaque groups.
  • Malignant pleural mesothelioma group: median HMGB1 60.23 ng/mL, significantly higher than the control, exposed, and pleural plaque groups. It did not differ significantly from the asbestosis group.
  • Mesothelioma versus healthy controls: area under the curve 0.94. The 95% confidence interval is printed as 0.89 to 0.99 in Table 3 and as 0.89 to 1.03 in the text. The best cut-off of 52.16 ng/mL gave 100% sensitivity and 80.28% specificity.
  • Mesothelioma versus exposed subjects: area under the curve 0.81 (95% CI 0.73 to 0.90) against those exposed under 10 years, with a cut-off of 52.29 ng/mL giving 100% sensitivity and 57.65% specificity. Against those exposed 10 years or more it was 0.80 (95% CI 0.72 to 0.89), with a cut-off of 52.39 ng/mL giving 100% sensitivity and 57.36% specificity.
  • Asbestosis versus other groups: area under the curve 0.88 (95% CI 0.82 to 0.95) against healthy controls, with a cut-off of 47.11 ng/mL giving 93.55% sensitivity and 70.42% specificity. Against those exposed under 10 years it was 0.74 (95% CI 0.66 to 0.83), and against those exposed 10 years or more it was 0.74 (95% CI 0.64 to 0.83).
  • Pleural plaques versus healthy controls: area under the curve 0.68 (95% CI 0.60 to 0.77), with a cut-off of 47.01 ng/mL giving 59.26% sensitivity and 70.42% specificity.
  • Mesothelioma versus asbestosis: area under the curve 0.56 (95% CI 0.39 to 0.73, P = 0.5043). The authors stated that serum HMGB1 is not useful for telling mesothelioma patients apart from asbestosis patients.
  • In regression analysis, belonging to the exposed, pleural plaque, asbestosis or mesothelioma groups was significantly and positively associated with serum HMGB1. No significant differences were found between groups of potential exposure level (P = 0.43) or exposure duration (P = 0.84).
  • Serum MMP2 and MMP9 were not correlated with HMGB1 in the pleural plaque, asbestosis or mesothelioma groups. Some positive correlations were found in the healthy and exposed groups.
• The authors' conclusion: The authors concluded that serum HMGB1 was significantly elevated in asbestos-exposed and asbestos-related disease subjects. They also concluded that it is a sensitive and specific biomarker to distinguish asbestosis and malignant mesothelioma from healthy or asbestos-exposed individuals.
• Limitations the authors state:
  • The authors stated that the low area under the curve (0.56) when comparing mesothelioma with asbestosis patients limits HMGB1's clinical usefulness for identifying different types of asbestos-related disease, and that accurately distinguishing the two requires further investigation.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis, Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: High Mobility Group Box 1 (HMGB1), Biomarker, Cytokine, Pleural Plaques, Malignant Mesothelioma.

Related studies

• HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma — Y. Wang, Z. Jiang, et al. (2019)
• Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China — Z. Jiang, W. Shen, et al. (2020)
• Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population — Z. Jiang, S. Ying, et al. (2017)
• HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients — A. Napolitano, D.J. Antoine, et al. (2016)
• Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma — C. Tabata, E. Shibata, et al. (2013)
• Serum HMGB1 as a diagnostic marker for malignant peritoneal mesothelioma — C. Tabata, S. Kanemura, et al. (2013)

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