HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients.

Abstract

PURPOSE:

To determine whether serum levels of high mobility group box protein 1 (HMGB1) could differentiate malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls.

EXPERIMENTAL DESIGN:

Hyperacetylated and nonacetylated HMGB1 (together referred to as total HMGB1) were blindly measured in blood collected from malignant mesothelioma patients (n = 22), individuals with verified chronic asbestos exposure (n = 20), patients with benign pleural effusions (n = 13) or malignant pleural effusions not due to malignant mesothelioma (n = 25), and healthy controls (n = 20). Blood levels of previously proposed malignant mesothelioma biomarkers fibulin-3, mesothelin, and osteopontin were also measured in nonhealthy individuals.

RESULTS:

HMGB1 serum levels reliably distinguished malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls. Total HMGB1 was significantly higher in malignant mesothelioma patients and asbestos-exposed individuals compared with healthy controls. Hyperacetylated HMGB1 was significantly higher in malignant mesothelioma patients compared with asbestos-exposed individuals and healthy controls, and did not vary with tumor stage. At the cut-off value of 2.00 ng/mL, the sensitivity and specificity of serum hyperacetylated HMGB1 in differentiating malignant mesothelioma patients from asbestos-exposed individuals and healthy controls was 100%, outperforming other previously proposed biomarkers. Combining HMGB1 and fibulin-3 provided increased sensitivity and specificity in differentiating malignant mesothelioma patients from patients with cytologically benign or malignant non-mesothelioma pleural effusion.

CONCLUSIONS:

Our results are significant and clinically relevant as they provide the first biomarker of asbestos exposure and indicate that hyperacetylated HMGB1 is an accurate biomarker to differentiate malignant mesothelioma patients from individuals occupationally exposed to asbestos and unexposed controls. A trial to independently validate these findings will start soon. Clin Cancer Res; 22(12); 3087-96. ©2016 AACR.

• Authors: Andrea Napolitano, Daniel J Antoine, Laura Pellegrini, Francine Baumann, Ian Pagano, Sandra Pastorino, Chandra M Goparaju, Kirill Prokrym, Claudia Canino, Harvey I Pass, Michele Carbone, Haining Yang
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 22 Issue 12 Pg. 3087-96 (06 15 2016) ISSN: 1557-3265 [Electronic] United States
• PMID: 26733616 (Publication Type: Journal Article)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Biomarkers
• EFEMP1 protein, human
• Extracellular Matrix Proteins
• GPI-Linked Proteins
• HMGB1 Protein
• HMGB1 protein, human
• SPP1 protein, human
• Osteopontin
• Asbestos
• Mesothelin

Topics

• Acetylation
• Adult
• Aged
• Asbestos (blood, toxicity)
• Biomarkers (blood)
• Environmental Exposure
• Extracellular Matrix Proteins (blood)
• Female
• GPI-Linked Proteins (blood)
• HMGB1 Protein (blood, metabolism)
• Humans
• Lung Neoplasms (blood, diagnosis)
• Male
• Mesothelin
• Mesothelioma (blood, diagnosis)
• Mesothelioma, Malignant
• Middle Aged
• Osteopontin (blood)
• Pleural Effusion (blood, diagnosis)
• Pleural Neoplasms (blood, diagnosis)
• Sensitivity and Specificity
• Young Adult