Department of Respiratory Medicine, Aalborg University Hospital, Aalborg, Denmark; Department of Oncology & Clinical Cancer Research Center, Aalborg University Hospital, DK-9000 Aalborg, Denmark.
Institute of Pathology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, DK-9000 Aalborg, Denmark.
Cancer Treat Rev. 2015 Jun;41(6):486-95. doi: 10.1016/j.ctrv.2015.05.001. Epub 2015 May 8.
Malignant pleural mesothelioma (MPM) is an asbestos-related cancer with a median survival of 12months. The MPM incidence is 1-6/100,000 and is increasing as a result of historic asbestos exposure in industrialized countries and continued use of asbestos in developing countries. Lack of accurate biomarkers makes diagnosis, prognostication and treatment prediction of MPM challenging. The aim of this review is to identify the front line of MPM biomarkers with current or potential clinical impact. Literature search using the PubMed and PLoS One databases, the related-articles function of PubMed and the reference lists of associated publications until April 26th 2015 revealed a plethora of candidate biomarkers. The current gold standard of MPM diagnosis is a combination of two positive and two negative immunohistochemical markers in the epithelioid and biphasic type, but sarcomatous type do not have specific markers, making diagnosis more difficult. Mesothelin in serum and pleural fluid may serve as adjuvant diagnostic with high specificity but low sensitivity. Circulating proteomic and microRNA signatures, fibulin-3, tumor cell gene-ratio test, transcriptomic, lncRNA, glycopeptides, pleural fluid FISH assay, hyaluronate/N-ERC mesothelin and deformability cytometry may be important future markers. Putative predictive markers for pemetrexed-platinum are tumor TS and TYMS, for vinorelbine the ERCC1, beta-tubuline class III and BRCA1. Mutations of the BAP1 gene are potential markers of MPM susceptibility. In conclusion, the current status of MPM biomarkers is not satisfactory but encouraging as more sensitive and specific non-invasive markers are emerging. However, prospective validation is needed before clinical application.
恶性胸膜间皮瘤（MPM）是一种与石棉有关的癌症，中位生存期为 12 个月。MPM 的发病率为 1-6/10 万，由于工业化国家历史上的石棉暴露和发展中国家继续使用石棉，发病率正在上升。缺乏准确的生物标志物使得 MPM 的诊断、预后和治疗预测具有挑战性。本综述的目的是确定具有当前或潜在临床影响的 MPM 生物标志物的前沿。使用 PubMed 和 PLoS One 数据库进行文献检索，PubMed 的相关文章功能和相关出版物的参考文献列表，直到 2015 年 4 月 26 日，揭示了大量候选生物标志物。目前 MPM 诊断的金标准是上皮样和双相型的两种阳性和两种阴性免疫组织化学标志物的组合，但肉瘤型没有特异性标志物，使诊断更加困难。血清和胸腔液中的间皮素可能作为辅助诊断标志物，具有高特异性但低灵敏度。循环蛋白组学和 microRNA 特征、纤维蛋白 3、肿瘤细胞基因比试验、转录组学、lncRNA、糖肽、胸腔液 FISH 检测、透明质酸/N-ERC 间皮素和变形细胞术可能是重要的未来标志物。培美曲塞-铂的潜在预测标志物是肿瘤 TS 和 TYMS，对于长春瑞滨，ERCC1、β-微管蛋白 III 类和 BRCA1。BAP1 基因突变可能是 MPM 易感性的标志物。总之，目前 MPM 生物标志物的状况不尽如人意，但令人鼓舞的是，越来越多的敏感和特异性非侵入性标志物正在出现。然而，在临床应用之前需要进行前瞻性验证。
