title: HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients.
abstract: To determine whether serum levels of high mobility group box protein 1 (HMGB1) could differentiate malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii. Department of Molecular Biosciences and Bioengineering, University of Hawaii at Mānoa, Honolulu, Hawaii.
authors.forename: Andrea
authors.initials: A
authors.lastname: Napolitano
authors.affiliation: MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Antoine
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii.
authors.forename: Laura
authors.initials: L
authors.lastname: Pellegrini
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii.
authors.forename: Francine
authors.initials: F
authors.lastname: Baumann
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii.
authors.forename: Ian
authors.initials: I
authors.lastname: Pagano
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pastorino
authors.affiliation: Department of Cardiothoracic Surgery, New York University, NYU Langone Medical Center, New York, New York.
authors.forename: Chandra M
authors.initials: CM
authors.lastname: Goparaju
authors.affiliation: Department of Cardiothoracic Surgery, New York University, NYU Langone Medical Center, New York, New York.
authors.forename: Kirill
authors.initials: K
authors.lastname: Prokrym
authors.affiliation: Department of Cardiothoracic Surgery, New York University, NYU Langone Medical Center, New York, New York.
authors.forename: Claudia
authors.initials: C
authors.lastname: Canino
authors.affiliation: Department of Cardiothoracic Surgery, New York University, NYU Langone Medical Center, New York, New York. hyang@cc.hawaii.edu mcarbone@cc.hawaii.edu Harvey.Pass@nyumc.org.
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Pass
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii. hyang@cc.hawaii.edu mcarbone@cc.hawaii.edu Harvey.Pass@nyumc.org.
authors.forename: Michele
authors.initials: M
authors.lastname: Carbone
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii. hyang@cc.hawaii.edu mcarbone@cc.hawaii.edu Harvey.Pass@nyumc.org.
authors.forename: Haining
authors.initials: H
authors.lastname: Yang
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D001194:Asbestos / Q000097:blood* / Q000633:toxicity; D015415:Biomarkers / Q000097:blood*; D004781:Environmental Exposure; D016326:Extracellular Matrix Proteins / Q000097:blood; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood; D024243:HMGB1 Protein / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis*; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood / Q000175:diagnosis*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood; D010996:Pleural Effusion / Q000097:blood / Q000175:diagnosis; D010997:Pleural Neoplasms / Q000097:blood / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers; C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C506895:SPP1 protein, human; D053495:Osteopontin; D001194:Asbestos; D000090204:Mesothelin