武汉云克隆科技股份有限公司

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. Hyperacetylated 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.

摘要：

目的：

探讨血清高迁移率族蛋白1(HMGB 1)是否能鉴别恶性间皮瘤患者、接触石棉者和阳性对照者。

方法：

从22例恶性间皮瘤患者，20例长期接触石棉者，13例良性胸腔积液患者，25例非恶性间皮瘤导致的恶性胸腔积液患者，20例阳性对照采集血液样本，盲法检测乙酰化和非乙酰化HMGB1(合称为总HMGB1)水平。在非健康个体血液中检测先前提出的恶性间皮瘤生物标记fibulin-3，间皮素和骨桥蛋白水平。

结果：

HMGB1血清水平可区分恶性间皮瘤患者、石棉接触者和阳性对照者。恶性间皮瘤患者和石棉接触者的总HMGB1水平明显高于阳性对照组。在恶性间皮瘤患者中乙酰化HMGB1水平明显高于石棉接触者和阳性对照者，且不随肿瘤分期而改变。血清乙酰化HMGB1在2.00ng/mL范围内鉴别恶性间皮瘤患者与石棉接触者及阳性对照的敏感特异性达到100%，优于其他先前提出的生物标记物。联合应用HMGB1和fibulin-3可以提高鉴别细胞学良性—恶性间皮瘤患者或恶性非间皮瘤胸腔积液患者的敏感性和特异性。

结论：

我们的结果具有重要的临床意义，它们提供了石棉接触的第一个生物标记，并且表明过乙酰化HMGB1是鉴别恶性间皮瘤患者最准确的生物标记。一项独立验证此发现的试验即将展开。

使用试剂原文信息：Plasma levels of fibulin-3 (USCN, Wuhan, PRC), mesothelin (R&D, Minneapolis, MN), and OPN (R&D, Minneapolis, MN) were measured in MM patients and asbestos-exposed individuals with indicated commercially available ELISA kits following manufactures’ instructions.