Protein Profiling of Pleural Effusions to Identify Malignant Pleural Mesothelioma Using SELDI-TOF MS

• Published in: Technology in cancer research & treatment Vol. 8; no. 5; pp. 323 - 332
• Main Authors: Hegmans, Joost P.J.J., Veltman, Joris D., Fung, Eric T., Verch, Thorsten, Glover, Curtis, Zhang, Fujun, Allard, W. Jeffrey, T'Jampens, Davy, Hoogsteden, Henk C., Lambrecht, Bart N., Aerts, Joachim
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-10-2009; Adenine Press
• Subjects: Adult; Aged; Aged, 80 and over; Apolipoprotein C-I - analysis; Area Under Curve; Biological and medical sciences; Biomarkers, Tumor - analysis; Female; Humans; Immunoassay; Male; Medical sciences; Mesothelioma - chemistry; Mesothelioma - diagnosis; Middle Aged; Neoplasm Proteins - analysis; Neoplasm Staging; Pleural Effusion, Malignant - chemistry; Pleural Effusion, Malignant - diagnosis; Pneumology; Prognosis; Protein Array Analysis; Proteome - analysis; Sensitivity and Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tumors of the respiratory system and mediastinum; Human; Respiratory disease; Biological marker; Malignant tumor; Malignant pleural effusion; Protein; Seldi Tof mass spectrometry; Cancerology; Pleurisy; Pleural disease; Diagnosis; Malignant pleural mesothelioma; Cancer
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/153303460900800502

Diagnosis of malignant pleural mesothelioma (MM) is limited. Novel proteomic technologies 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.