Serum HMGB1 as a diagnostic marker for malignant peritoneal mesothelioma

Our plain-English summary of Serum HMGB1 as a diagnostic marker for malignant peritoneal mesothelioma, by C. Tabata, S. Kanemura, R. Tabata, et al (Journal of Clinical Gastroenterology, 2013).

The study

• Authors: C. Tabata, S. Kanemura, R. Tabata, E. Masachika, E. Shibata, T. Otsuki, T. Nishizaki, T. Nakano
• Journal: Journal of Clinical Gastroenterology
• Published: 2013;47(8):684-8
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intraperitoneal chemotherapy. Therefore, early diagnosis of DMPM is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. DMPM 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.

Study: The serum concentrations of HMGB1 were measured in 13 DMPM patients and 45 individuals with benign asbestos-related diseases.

Result: We demonstrated that the patients with DMPM had significantly higher serum levels of HMGB1 compared with the population who had been exposed to asbestos but did not develop DMPM.

Conclusion: Our data suggest that serum HMGB1 concentration is a useful serum marker for DMPM.

In plain English

This study, from Hyogo College of Medicine Hospital in Japan, measured a blood protein called HMGB1 in serum samples collected from 2005 to 2010. It compared 13 patients with diffuse malignant peritoneal mesothelioma (DMPM) with 45 asbestos-exposed people who did not have DMPM. Ten of the 13 patients had a documented asbestos exposure history. Of the 45, 26 had pleural plaques and/or asbestosis and 19 had no asbestos-related lesions. HMGB1 averaged 13.5 ± 12.7 ng/mL in the DMPM patients and 5.3 ± 1.7 ng/mL in the comparison group, a statistically significant difference. At a cutoff of 8.0 ng/mL, the test identified 53.8% of DMPM patients (sensitivity) and correctly classified 97.8% of the comparison group as negative (specificity). HMGB1 levels did not differ significantly between the DMPM patients and 10 patients with other cancers. A second marker, mesothelin, showed a better AUC and sensitivity in the same groups. The authors concluded that HMGB1 would be a useful serum diagnostic factor for DMPM, but that it might not distinguish DMPM from other cancers.

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: Hospital-based diagnostic marker study comparing serum HMGB1 levels between patients with DMPM and asbestos-exposed people without DMPM, using ROC curve analysis
• Who was studied: 58 people seen at the Department of Respiratory Medicine of Hyogo College of Medicine Hospital, Japan, from 2005 to 2010. Of these, 13 had diffuse malignant peritoneal mesothelioma (12 diagnosed from tissue samples and 1 from cytologic samples). The other 45 were asbestos-exposed people without DMPM: 26 had pleural plaques and/or asbestosis and 19 had no asbestos-related lesions. For further comparison, sera were also collected from 10 patients with other cancers and from 5 healthy volunteers never exposed to asbestos.
• Exposure: Documented asbestos exposure history, held by all 45 non-DMPM subjects and by 10 of the 13 DMPM patients. No fiber types, jobs or doses were given.
• Main results:
  • Serum HMGB1 was significantly higher in DMPM patients (13.5 ± 12.7 ng/mL) than in the asbestos-exposed non-DMPM group with benign asbestos-related diseases or no lesions (5.3 ± 1.7 ng/mL), P < 0.001
  • In distinguishing DMPM patients from the asbestos-exposed non-DMPM group, HMGB1 had an area under the ROC curve (AUC) of 0.821 (95% CI, 0.706-0.935)
  • At the optimal cutoff of 8.0 ng/mL, HMGB1 had a sensitivity of 53.8% and a specificity of 97.8%, with a positive predictive value of 87.5% and a negative predictive value of 88.0%
  • Among DMPM patients, differences in HMGB1 by tumor histology (epithelioid 9.2 ± 4.3 vs non-epithelioid 20.4 ± 18.9 ng/mL), sex, age group and performance status were not statistically significant
  • HMGB1 did not differ significantly between asbestos-exposed non-MPM subjects (5.3 ± 1.7 ng/mL) and 5 healthy volunteers never exposed to asbestos (5.6 ± 0.9 ng/mL)
  • HMGB1 did not differ significantly between DMPM patients (13.5 ± 12.7) and patients with other cancers (12.4 ± 10.0 ng/mL)
  • Serum mesothelin in the same comparison had an AUC of 0.870 (95% CI, 0.733-1.006). At a cutoff of 50.0 ng/mL its sensitivity was 84.6% and its specificity 97.2%. Mesothelin averaged 132.7 ± 88.0 ng/mL in DMPM patients versus 23.4 ± 14.4 ng/mL in the non-DMPM group (P < 0.001).
  • Serum HMGB1 and mesothelin levels in DMPM patients were not correlated (rs = 0.28, P = 0.33)
• The authors' conclusion: The authors concluded that patients with DMPM had significantly higher serum HMGB1 than asbestos-exposed people without DMPM, and suggested that HMGB1 would be a useful serum diagnostic factor for DMPM. They described this as the first report on serum HMGB1 and DMPM.
• Limitations the authors state:
  • The authors stated that HMGB1 might not be suitable for telling DMPM apart from other cancers, because levels did not differ significantly between those groups
  • The authors noted that the diagnostic sensitivity of HMGB1 was not high (53.8%)
  • The authors reported that mesothelin showed a better AUC and sensitivity than HMGB1 in this study

Topics

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

Medical terms in this study, explained in our Lexicon: High Mobility Group Box 1 (HMGB1), Peritoneal Mesothelioma, Cytoreductive Surgery, Chemotherapy, Pulmonary Fibrosis, Malignant Transformation, Mesothelial Cells, Fibroblast.

Related studies

• Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma — C. Tabata, E. Shibata, et al. (2013)
• Serum thioredoxin-1 as a diagnostic marker for malignant peritoneal mesothelioma — C. Tabata, T. Terada, et al. (2013)
• 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)

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