title: Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma.
abstract: BACKGROUND
  Pleural malignant mesothelioma (MM) is a deadly tumour predominantly associated with asbestos exposure. A reliable diagnostic and prognostic marker for MM will significantly enhance clinical care and is an area of intense research. Soluble mesothelin is the most studied and an FDA-approved biomarker for MM. A recent report showed promising results using fibulin-3 as a new diagnostic marker. The aim of this study was to compare the utility of fibulin-3 versus mesothelin, singly or in combination.
  
  
  METHODS
  Fibulin-3 and soluble mesothelin were determined by ELISA in the plasma and pleural fluid of 153 patients presenting with a pleural effusion including 82 with MM, 36 with non-MM malignant effusions and 35 with benign effusions. Biomarker concentrations were determined in the plasma of an additional 49 cases with benign asbestos-related disease.
  
  
  RESULTS
  Mesothelin provides better diagnostic accuracy than fibulin-3 for MM whether measured in plasma or pleural effusion: area under the curve (AUC) for plasma was 0.822 (95% CI 0.76 to 0.87) compared with 0.671 (0.61 to 0.73), respectively, and for pleural fluid AUC was 0.815 (0.74 to 0.87) compared with 0.588 (0.51 to 0.67), respectively. Effusion fibulin-3 was an independent significant prognostic factor for survival in MM patients; HR 2.08 (1.14 to 3.82), p=0.017. MM patients with effusion fibulin-3 levels below the median survived significantly longer than those with levels above the median (14.1 vs 7.9 months, p=0.012). Mesothelin and neutrophil to lymphocyte ratio were not significant prognostic markers.
  
  
  CONCLUSIONS
  Soluble mesothelin is a superior diagnostic biomarker for MM compared with fibulin-3, whereas fibulin-3 provides superior prognostic information compared with mesothelin.
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia The Australian Mesothelioma Tissue Bank, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors.forename: Jenette
authors.initials: J
authors.lastname: Creaney
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Dick
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Meniawy
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia The Australian Mesothelioma Tissue Bank, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors.forename: Su Lyn
authors.initials: SL
authors.lastname: Leong
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia The Australian Mesothelioma Tissue Bank, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors.forename: Justine S
authors.initials: JS
authors.lastname: Leon
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia The Australian Mesothelioma Tissue Bank, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Demelker
authors.affiliation: PathWest Laboratory Medicine WA, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Segal
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors.forename: A W Bill
authors.initials: AW
authors.lastname: Musk
authors.affiliation: Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia Centre for Asthma, Allergy and Respiratory Research, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Y C Gary
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Skates
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Nowak
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia The Australian Mesothelioma Tissue Bank, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors.forename: Bruce W S
authors.initials: BW
authors.lastname: Robinson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D001706:Biopsy; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000378:metabolism* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D000090204:Mesothelin
keywords: Mesothelioma