Imaging Mass Spectrometry in Papillary Thyroid Carcinoma for the Identification and Validation of Biomarker Proteins

다국어 초록 (Multilingual Abstract)

Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorptionionization and time-of-flight (MALDI-TOF) mass spectrometry has become increasinglyimportant in biology and medicine, because this technology can detect the relativeabundance and spatial distribution of interesting proteins in tissues. Five thyroid cancersamples, along with normal tissue, were sliced and transferred onto conductive glass slides.
After laser scanning by MALDI-TOF equipped with a smart beam laser, images were createdfor individual masses and proteins were classified at 200-μm spatial resolution. Based onthe spatial distribution, region-specific proteins on a tumor lesion could be identified byprotein extraction from tumor tissue and analysis using liquid chromatography withtandem mass spectrometry (LC-MS/MS). Using all the spectral data at each spot, variousintensities of a specific peak were detected in the tumor and normal regions of the thyroid.
Differences in the molecular weights of expressed proteins between tumor and normalregions were analyzed using unsupervised and supervised clustering. To verify the presenceof discovered proteins through IMS, we identified ribosomal protein P2, which is specificfor cancer. We have demonstrated the feasibility of IMS as a useful tool for the analysis oftissue sections, and identified the tumor-specific protein ribosomal protein P2.

참고문헌 (Reference)

• 1 Meding S, "Tumor classification of six common cancer types based on proteomic profiling by MALDI imaging" 11 : 1996-2003, 2012
• 2 Lemaire R, "Specific MALDI imaging and profiling for biomarker hunting and validation: fragment of the 11S proteasome activator complex, Reg alpha fragment, is a new potential ovary cancer biomarker" 6 : 4127-4134, 2007
• 3 Gardner-Thorpe J, "Ribosomal protein P2 : a potential molecular target for antisense therapy of human malignancies" 23 : 4549-4560, 2003
• 4 Kwang Hyun Ko, "Recent Advances in Molecular Imaging of Premalignant Gastrointestinal Lesions and Future Application for Early Detection of Barrett Esophagus" 대한소화기내시경학회 47 (47): 7-14, 2014
• 5 Chaurand P, "Proteomics in diagnostic pathology : profiling and imaging proteins directly in tissue sections" 165 : 1057-1068, 2004
• 6 Schwartz SA, "Proteomic-based prognosis of brain tumor patients using direct-tissue matrix-assisted laser desorption ionization mass spectrometry" 65 : 7674-7681, 2005
• 7 Yanagisawa K, "Proteomic patterns of tumour subsets in non-small-cell lung cancer" 362 : 433-439, 2003
• 8 Kang HS, "Protein and lipid MALDI profiles classify breast cancers according to the intrinsic subtype" 11 : 465-, 2011
• 9 Santarpia L, "Phosphatidylinositol 3-kinase/akt and ras/raf-mitogen-activated protein kinase pathway mutations in anaplastic thyroid cancer" 93 : 278-284, 2008
• 10 Kondo T, "Pathogenetic mechanisms in thyroid follicular-cell neoplasia" 6 : 292-306, 2006
• 11 Mazzaferri EL, "Management of a solitary thyroid nodule" 328 : 553-559, 1993
• 12 Shimma S, "MALDI-based imaging mass spectrometry revealed abnormal distribution of phospholipids in colon cancer liver metastasis" 855 : 98-103, 2007
• 13 Seeley EH, "MALDI imaging mass spectrometry of human tissue : method challenges and clinical perspectives" 29 : 136-143, 2011
• 14 Walch A, "MALDI imaging mass spectrometry for direct tissue analysis : a new frontier for molecular histology" 130 : 421-434, 2008
• 15 Balluff B, "MALDI imaging identifies prognostic seven-protein signature of novel tissue markers in intestinal-type gastric cancer" 179 : 2720-2729, 2011
• 16 Seeley EH, "Imaging mass spectrometry : towards clinical diagnostics" 2 : 1435-1443, 2008
• 17 Chaurand P, "Imaging mass spectrometry : principles and potentials" 33 : 92-101, 2005
• 18 Adeniran AJ, "Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas" 30 : 216-222, 2006
• 19 Shanta SR, "Binary matrix for MALDI imaging mass spectrometry of phospholipids in both ion modes" 83 : 1252-1259, 2011
• 20 Xing M, "BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications" 28 : 742-762, 2007
• 21 고광현, "Application of Matrix-Assisted Laser Desorption/lonization Time-of-Flight Imaging Mass Spectrometry (MALDI-TOF IMS) for Permalignant Gastrointestinal Lesions Premalignant Lesions" 대한소화기내시경학회 46 (46): 611-619, 2013
• 22 Kang S, "Alteration in lipid and protein profiles of ovarian cancer: similarity to breast cancer" 21 : 1566-1572, 2011
• 23 Cornett DS, "A novel histology-directed strategy for MALDI-MS tissue profiling that improves throughput and cellular specificity in human breast cancer" 5 : 1975-1983, 2006