Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma

Our plain-English summary of Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma, by C. Tabata, E. Shibata, R. Tabata, et al (BMC Cancer, 2013).

The study

• Authors: C. Tabata, E. Shibata, R. Tabata, S. Kanemura, K. Mikami, Y. Nogi, E. Masachika, T. Nishizaki, T. Nakano
• Journal: BMC Cancer
• Published: 2013;13:205
• Cited by: 59 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to conventional chemotherapy and radiotherapy. Therefore, diagnosing MPM early is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. MPM involves the malignant transformation of mesothelial cells, which originate from mesenchymal cells similar to lung fibroblasts. Here, we investigated serum levels of HMGB1 in patients with MPM and compared them with those of a population that had been exposed to asbestos without developing MPM.

Methods: HMGB1 production from MPM cell lines was measured using ELISA. Serum HMGB1 levels were also examined in 61 MPM patients and 45 individuals with benign asbestos-related diseases.

Results: HMGB1 concentrations of 2 out of 4 MPM cell lines were higher than that of normal mesothelial cell line, Met-5A. We demonstrated that patients with MPM had significantly higher serum levels of HMGB1 than the population who had been exposed to asbestos but had not developed MPM. The difference in overall survival between groups with serum HMGB1 levels that were lower and higher than assumed cut-off values was significant.

Conclusions: Our data suggest that serum HMGB1 concentration is a useful prognostic factor for MPM.

In plain English

The authors measured a blood protein, HMGB1, in people with documented asbestos exposure seen at Hyogo College of Medicine Hospital, Japan, from 2005 to 2009. Serum from 61 patients with malignant pleural mesothelioma was compared with serum from 45 people without it (26 with pleural plaques and/or asbestosis, 19 with no asbestos-related lesions). Median HMGB1 was 6.7 ng/ml in the mesothelioma patients and 5.4 ng/ml in the others (p=0.001). At a cut-off of 9.0 ng/ml, 34.4% of mesothelioma patients were above it, a sensitivity the authors called not high, and specificity was 100%. Levels did not differ significantly between sarcomatoid and other tumors, across stages, or versus 11 lung cancer patients with malignant pleural effusion. Overall survival differed significantly between mesothelioma patients below (40) and above (21) the cut-off (p=0.03). In multivariate analysis, the hazard ratio for high HMGB1 was 2.1 (95% CI 1.0-4.4; p=0.05). In laboratory tests, two of four mesothelioma cell lines produced more HMGB1 than a normal mesothelial cell line. The authors suggested HMGB1 might be a useful prognostic marker and called for further study.

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: Laboratory cell-line experiment combined with a hospital-based comparison of serum HMGB1 levels between patients with and without mesothelioma, plus survival analysis (Kaplan-Meier and Cox regression) in the mesothelioma patients
• Who was studied: 106 people with documented asbestos exposure who presented at the Department of Respiratory Medicine, Hyogo College of Medicine Hospital, Japan, from 2005 to 2009. Of these, 61 had malignant pleural mesothelioma and 45 did not (26 with pleural plaques and/or asbestosis, 19 with no asbestos-related lesions). Also 11 patients with lung cancer involving malignant pleural effusion, and four mesothelioma cell lines plus one normal mesothelial cell line (MeT-5A).
• Exposure: All participants had a documented history of asbestos exposure; fiber types, sources and amounts were not described. The factor studied was serum HMGB1 level, using a cut-off of 9.0 ng/ml.
• Main results:
  • Serum HMGB1 was significantly higher in mesothelioma patients (median 6.7, interquartile range 4.8-11.0 ng/ml) than in the non-mesothelioma asbestos-exposed group (median 5.4, interquartile range 4.0-6.7 ng/ml); p=0.001.
  • For distinguishing mesothelioma patients from non-mesothelioma subjects, the area under the ROC curve was 0.674 (95% CI 0.589-0.758). At a cut-off of 9.0 ng/ml, sensitivity was 34.4% and specificity was 100%.
  • Among mesothelioma patients, serum HMGB1 levels did not differ significantly between sarcomatoid and non-sarcomatoid histology (p=0.68), across disease stages, or by age.
  • Serum HMGB1 levels in mesothelioma patients did not differ significantly from those of 11 lung cancer patients with malignant pleural effusion (median 7.0, interquartile range 5.5-10.4 ng/ml; p=0.75).
  • The 61 mesothelioma patients were split by the 9.0 ng/ml cut-off: 40 below and 21 above. Overall survival differed significantly between the two groups (p=0.03).
  • In Cox regression on the 61 mesothelioma patients, adjusting for age, gender, histology and stage, serum HMGB1 of 9.0 ng/ml or more versus below 9.0 ng/ml had a hazard ratio of 2.1 (95% CI 1.0-4.4; p=0.05) for survival.
  • In the same Cox regression, stage IV versus stages I to III had a hazard ratio of 2.6 (95% CI 1.1-6.1; p=0.03) for survival.
  • In laboratory tests, mesothelioma cell lines H28 (epithelioid) and H2052 (sarcomatoid) produced significantly more HMGB1 than cell lines H2452 and MSTO-211H and the normal mesothelial cell line MeT-5A.
• The authors' conclusion: The authors suggested that serum HMGB1 might be a useful prognostic factor for malignant pleural mesothelioma.
• Limitations the authors state:
  • The authors noted that the diagnostic sensitivity of serum HMGB1 for mesothelioma was not high (34.4%).
  • The authors stated that further examination of serum HMGB1 in mesothelioma is needed, noting that serum mesothelin is currently considered the best available serum biomarker.

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), Pleural Mesothelioma, Chemotherapy, Pulmonary Fibrosis, Malignant Transformation, Mesothelial Cells, Fibroblast, Overall Survival.

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• Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases — S. Ying, Z. Jiang, 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)
• HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma — L. Pellegrini, J. Xue, et al. (2017)
• HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma — Y. Wang, Z. Jiang, et al. (2019)
• Serum thioredoxin-1 as a diagnostic marker for malignant peritoneal mesothelioma — C. Tabata, T. Terada, et al. (2013)

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