Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure. Its poor prognosis makes early diagnosis extremely important, which would provide an opportunity for early treatment and potentially changing outcomes. This study aimed to explore the underlying mechanisms of MM and discover novel noninvasive biomarkers for the diagnosis of malignant mesothelioma. Using Isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS), a total of 145 differentially expressed serum proteins were identified between MM patients and healthy controls. The identified proteins were further analyzed by bioinformatics, out of which three candidate biomarkers (Filamin A (FLNA), Fibulin 1 (FBLN1) and Thrombospondin-1 (TSP-1)) were validated in large cohorts of patients with asbestos-related diseases including MM patients by ELISA assay. Receiver operating characteristic (ROC) curve analysis showed that serum FLNA, FBLN1 and TSP-1 had high diagnostic values in distinguishing MM patients from healthy controls, individuals with asbestos exposure (AE), and patients with pleural plaques (PP) or asbestosis. Meanwhile, serum FBLN1 and TSP-1 possessed good diagnostic values in distinguishing asbestosis patients from healthy controls and individuals with AE. The combination of FLNA, FBLN1, and TSP-1 proteins had higher sensitivity and specificity in discriminating patients with MM, PP and asbestosis. Our findings indicated that analysis of serum proteome using iTRAQ is a feasible strategy for biomarker discovery, and serum FLNA, FBLN1 and TSP-1 may be promising candidates for diagnosis of malignant mesothelioma and screening of at-risk individuals.

恶性间皮瘤（MM）是与石棉接触有关的侵袭性癌症。它的不良预后使早期诊断极为重要，这将为早期治疗和可能改变预后提供机会。这项研究旨在探讨MM的潜在机制，并发现新的非侵入性生物标志物，用于诊断恶性间皮瘤。使用等压绝对和绝对定量标签（iTRAQ）并结合二维液相色谱/串联质谱（2D LC-MS / MS），在MM患者和健康对照之间共鉴定了145种差异表达的血清蛋白。通过生物信息学进一步分析鉴定出的蛋白质，其中三个候选生物标记（Filamin A（FLNA），通过ELISA分析，在包括石棉相关疾病在内的大批患者（包括MM患者）中验证了纤维蛋白1（FBLN1）和血小板反应蛋白-1（TSP-1）。接受者操作特征（ROC）曲线分析表明，血清FLNA，FBLN1和TSP-1在区分MM患者与健康对照，石棉暴露（AE）以及胸膜斑块（PP）或石棉沉着症患者方面具有较高的诊断价值。同时，血清FBLN1和TSP-1在区分石棉沉滞症患者与健康对照和AE患者中具有良好的诊断价值。FLNA，FBLN1和TSP-1蛋白的组合在区分MM，PP和石棉沉着症患者中具有更高的敏感性和特异性。我们的发现表明，使用iTRAQ分析血清蛋白质组是发现生物标记物的可行策略，而血清FLNA，