title: Protein profiling of pleural effusions to identify malignant pleural mesothelioma using SELDI-TOF MS.
abstract: Diagnosis of malignant pleural mesothelioma (MM) is limited. Novel proteomic techno_logies can be utilized to discover changes in expression of pleural proteins that might have diagnostic value. The objective of this study was to detect protein profiles that could be used to identify malignant pleural mesothelioma with surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS). Pleural effusions were collected from patients with confirmed mesothelioma (n = 41) and from patients with effusions due to other causes ([n = 48] cancerous and non-cancerous). Samples were fractionated using anion exchange chromatography and bound to different types of ProteinChip array surfaces. All samples were also subjected to other commercially available immunoassays (human epididymes protein 4 [HE4], osteopontin [OPN], soluble mesothelin-related proteins [SMRP], and the cytokeratin 19 fragment [CYFRA 21-1]). Peak intensity data obtained by SELDI-TOF were subjected to classification algorithms in order to identify potential classifier peaks. A protein peak at m/z 6614 was characterized as apolipoprotein (Apo) CI. In this setting, the sensitivity and specificity of this potential biomarker was 76 % and 69 %, respectively. The area under the receiver operating characteristic curve (AUC) for Apo CI was 0.755, thereby outperforming OPN, HE4, and CYFRA 21-1. SMRP performed best with an AUC of 0.860 with a sensitivity of 83% and specificity of 74%. Our study validates the use of SMRP as a diagnostic marker for pleural mesothelioma and furthermore suggests that Apo CI levels could be used in the future to discriminate pleural mesothelioma from other causes of exudates.
authors.affiliation: Department of Pulmonary Medicine Erasmus MC, Dr. Molewaterplein 50 3015 GE Rotterdam, The Netherlands. j.hegmans@erasmusmc.nl
authors.forename: Joost P J J
authors.initials: JP
authors.lastname: Hegmans
authors.forename: Joris D
authors.initials: JD
authors.lastname: Veltman
authors.forename: Eric T
authors.initials: ET
authors.lastname: Fung
authors.forename: Thorsten
authors.initials: T
authors.lastname: Verch
authors.forename: Curtis
authors.initials: C
authors.lastname: Glover
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
authors.forename: W Jeffrey
authors.initials: WJ
authors.lastname: Allard
authors.forename: Davy
authors.initials: D
authors.lastname: T'Jampens
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: Joachim
authors.initials: J
authors.lastname: Aerts
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053302:Apolipoprotein C-I / Q000032:analysis*; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007118:Immunoassay; D008297:Male; D008654:Mesothelioma / Q000737:chemistry / Q000175:diagnosis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D016066:Pleural Effusion, Malignant / Q000737:chemistry / Q000175:diagnosis*; D011379:Prognosis; D040081:Protein Array Analysis; D020543:Proteome / Q000032:analysis; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D053302:Apolipoprotein C-I; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome