HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma

Our plain-English summary of HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma, by Y. Wang, Z. Jiang, J. Yan, et al (Disease Markers, 2019).

The study

• Authors: Y. Wang, Z. Jiang, J. Yan, S. Ying
• Journal: Disease Markers
• Published: 2019;2019:4183157
• Type of article: Review
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a rare, aggressive, and highly lethal cancer that is substantially induced by exposure to asbestos fibers. High-mobility group box 1 (HMGB1) is an intriguing proinflammatory molecule involved in MM. In this review, we describe the possible crucial roles of HMGB1 in carcinogenic mechanisms based on in vivo and in vitro experimental evidence and outline the clinical findings of epidemiological investigations regarding the possible roles of HMGB1 as a biomarker for MM. We conclude that novel strategies targeting HMGB1 may suppress MM cells and interfere with asbestos-induced inflammation.

In plain English

This article was a review, not a new study. The authors summarized published laboratory, animal and human research on HMGB1, an inflammation-related protein, in malignant mesothelioma. They described experiments in which crocidolite asbestos caused human mesothelial cells to die and release HMGB1. In mice, the HMGB1 rise caused by chrysotile was temporary. They outlined human blood studies. One, from the United States, reported mean serum HMGB1 of 80.2 ng/ml in asbestos-exposed people versus 16.9 ng/ml in nonexposed controls. Another was the authors' own earlier study in a Chinese Han population, with median levels of about 50 ng/ml in exposed groups and 41.68 ng/ml in healthy controls. How accurately HMGB1 separated mesothelioma patients from others varied by study. In the Chinese study, its accuracy in separating pleural mesothelioma patients from asbestos-exposed people was what the authors called very low. They also reviewed approaches tested only in cells and mice, such as aspirin. The authors concluded that strategies targeting HMGB1 may suppress mesothelioma cells. They noted that many other inflammatory conditions also raise HMGB1.

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: Review of published in vivo (animal), in vitro (cell) and epidemiological studies on HMGB1 in malignant mesothelioma
• Who was studied: No new population was studied. The review covered cell-line and animal studies, plus human blood and tissue studies from the United States, Japan, China (Chinese Han population) and Italy.
• Exposure: Asbestos, mainly crocidolite and chrysotile in experimental models. In human studies, asbestos exposure was grouped by duration (under 10 years and 10 years or more) in the authors' earlier Chinese study.
• Main results:
  • Reviewed cell study (Yang et al.): crocidolite asbestos induced programmed necrosis in primary human mesothelial cells, and HMGB1 was released.
  • Reviewed mouse experiments: the HMGB1 increase caused by chrysotile was transient, returning to background within 6 to 10 weeks.
  • Reviewed US study: mean serum HMGB1 was 80.2 ng/ml in asbestos-exposed individuals, significantly higher than in heavy smokers (26.1 ng/ml) and nonexposed controls (16.9 ng/ml).
  • Authors' earlier Chinese Han study: median serum HMGB1 was 50.06 ng/ml in people exposed under 10 years and 50.42 ng/ml in those exposed 10 years or more. Both were significantly higher than 41.68 ng/ml in healthy controls. There was no significant difference between the two exposure-duration groups.
  • Reviewed Japanese studies (Tabata et al.): diagnostic AUCs of 0.674 (95% CI 0.589 to 0.758) for malignant pleural mesothelioma and 0.821 (95% CI 0.706 to 0.935) for diffuse malignant peritoneal mesothelioma.
  • Authors' earlier Chinese Han study: the AUC comparing malignant pleural mesothelioma patients with asbestos-exposed individuals was 0.56 (95% CI 0.39 to 0.73), which the authors called very low.
  • Reviewed study (Napolitano et al.): hyperacetylated HMGB1, but not total HMGB1, discriminated mesothelioma patients from asbestos-exposed individuals or healthy controls with 100% specificity and sensitivity.
  • Reviewed preclinical work: aspirin and its metabolite salicylic acid reduced extracellular HMGB1 secreted by human mesothelioma cells. In mice injected with human mesothelioma cells, HMGB1 Box-A reduced tumor growth.
• The authors' conclusion: The authors concluded that new strategies targeting HMGB1 may suppress mesothelioma cells and interfere with asbestos-induced inflammation. They also concluded that combining HMGB1 with other biomarkers and radiographic findings may help identify mesothelioma in asbestos-exposed populations.
• Limitations the authors state:
  • Many inflammation-associated diseases or outside factors also raise HMGB1 levels.
  • In one reviewed study, serum HMGB1 did not differ significantly between pleural mesothelioma patients and lung cancer patients with malignant pleural effusion.
  • HMGB1 isoforms can currently be measured only by liquid chromatography-tandem mass spectrometry.
  • HMGB1 levels may vary by ethnicity, sample storage times and experimental conditions.
  • The link between HMGB1 and survival needs more evidence from larger numbers of tissue samples.

Topics

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

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

Related studies

• Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases — S. Ying, Z. Jiang, et al. (2017)
• HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma — L. Pellegrini, J. Xue, 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)
• 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)
• Preventive and therapeutic opportunities: targeting BAP1 and/or HMGB1 pathways to diminish the burden of mesothelioma — M. Carbone, M. Minaai, et al. (2023)
• Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma — C. Tabata, E. Shibata, et al. (2013)

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