title: The established and future biomarkers of malignant pleural mesothelioma.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, Aalborg University Hospital, Aalborg, Denmark; Department of Oncology & Clinical Cancer Research Center, Aalborg University Hospital, DK-9000 Aalborg, Denmark. Electronic address: vasiliki_panou@hotmail.com.
authors.forename: V
authors.initials: V
authors.lastname: Panou
authors.affiliation: Institute of Pathology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, DK-9000 Aalborg, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Vyberg
authors.affiliation: Department of Respiratory Medicine, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, DK-9000 Aalborg, Denmark.
authors.forename: U M
authors.initials: UM
authors.lastname: Weinreich
authors.affiliation: Institute of Pathology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Meristoudis
authors.affiliation: Department of Oncology & Clinical Cancer Research Center, Aalborg University Hospital, DK-9000 Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, DK-9000 Aalborg, Denmark.
authors.forename: U G
authors.initials: UG
authors.lastname: Falkmer
authors.affiliation: Department of Oncology & Clinical Cancer Research Center, Aalborg University Hospital, DK-9000 Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, DK-9000 Aalborg, Denmark; Cancer Clinic, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: oluf.roe@ntnu.no.
authors.forename: O D
authors.initials: OD
authors.lastname: Røe
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D064032:Calbindin 2 / Q000032:analysis; D016326:Extracellular Matrix Proteins / Q000032:analysis; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis; D007150:Immunohistochemistry; D053555:Keratin-5 / Q000032:analysis; D008175:Lung Neoplasms / Q000175:diagnosis*; D008562:Membrane Glycoproteins / Q000032:analysis; D008654:Mesothelioma / Q000175:diagnosis*; D000086002:Mesothelioma, Malignant; D035683:MicroRNAs / Q000032:analysis; D010997:Pleural Neoplasms / Q000175:diagnosis*; D025521:Tumor Suppressor Proteins / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D025721:WT1 Proteins / Q000032:analysis; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D064032:Calbindin 2; D016326:Extracellular Matrix Proteins; D006820:Hyaluronic Acid; D053555:Keratin-5; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase; D025721:WT1 Proteins; C400134:BAP1 protein, human; C576764:CALB2 protein, human; C119630:EFEMP1 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin; C583751:WT1 protein, human
keywords: BAP-1; Gene-ratio; Immunohistochemistry; Mesothelin; MicroRNA; lncRNA