HMGB1 and its hyper-acetylated isoform are sensitive and specific serum biomarkers to detect asbestos exposure and to identify mesothelioma patients
Clinical Cancer Research 2016 January 5 [Epub ahead of print] [Link]
Napolitano A, Antoine DJ, Pellegrini L, Baumann F, Pagano IS, Pastorino S, Goparaju CM, Prokrym K, Canino C, Pass H, Carbone M, Yang H.
Abstract
Purpose
To determine whether serum levels of High Mobility Group Box Protein-1 (HMGB1) could differentiate malignant mesothelioma (MM) patients, asbestos-exposed individuals, and unexposed controls.
Experimental Design
Hyper-acetylated and non-acetylated HMGB1 (together referred to as total HMGB1) were blindly measured in blood collected from MM 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 MM (n=25), and healthy controls (n=20). Blood levels of previously proposed MM biomarkers fibulin-3, mesothelin, and osteopontin were also measured in non-healthy individuals.
Results
HMGB1 serum levels reliably distinguished MM patients, asbestos-exposed individuals, and unexposed controls. Total HMGB1 was significantly higher in MM patients and asbestos-exposed individuals compared to healthy controls. Hyper-acetylated HMGB1 was significantly higher in MM patients compared to 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 hyper-acetylated HMGB1 in differentiating MM 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 MM patients from patients with cytologically benign or malignant non-MM pleural effusion.
Conclusions
Our results are significant and clinically relevant as they provide the first biomarker of asbestos exposure and indicate that hyper-acetylated HMGB1 is an accurate biomarker to differentiate MM patients from individuals occupationally exposed to asbestos and unexposed controls. A trial to independently validate these findings will start soon.
