title: Imaging mass spectrometry in papillary thyroid carcinoma for the identification and validation of biomarker proteins.
abstract: Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization and time-of-flight (MALDI-TOF) mass spectrometry has become increasingly important in biology and medicine, because this technology can detect the relative abundance and spatial distribution of interesting proteins in tissues. Five thyroid cancer samples, 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 created for individual masses and proteins were classified at 200-µm spatial resolution. Based on the spatial distribution, region-specific proteins on a tumor lesion could be identified by protein extraction from tumor tissue and analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using all the spectral data at each spot, various intensities 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 normal regions were analyzed using unsupervised and supervised clustering. To verify the presence of discovered proteins through IMS, we identified ribosomal protein P2, which is specific for cancer. We have demonstrated the feasibility of IMS as a useful tool for the analysis of tissue sections, and identified the tumor-specific protein ribosomal protein P2.
authors.affiliation: Department of Pathology, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Kyueng-Whan
authors.identifier: 0000-0002-4757-9211
authors.initials: KW
authors.lastname: Min
authors.affiliation: Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul, Korea. ; SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea.
authors.forename: Joo-Young
authors.identifier: 0000-0002-2314-1530
authors.initials: JY
authors.lastname: Bang
authors.affiliation: Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul, Korea. ; SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea.
authors.forename: Kwang Pyo
authors.identifier: 0000-0003-0095-3787
authors.initials: KP
authors.lastname: Kim
authors.affiliation: Department of Pathology, Konkuk University School of Medicine, Seoul, Korea. ; The Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Wan-Seop
authors.identifier: 0000-0001-7704-5942
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Department of Pathology, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Sang Hwa
authors.identifier: 0000-0003-2692-9881
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul, Korea.
authors.forename: Selina Rahman
authors.identifier: 0000-0003-0602-1323
authors.initials: SR
authors.lastname: Shanta
authors.affiliation: Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul, Korea.
authors.forename: Jeong Hwa
authors.identifier: 0000-0001-9787-6591
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul, Korea.
authors.forename: Ji Hye
authors.identifier: 0000-0001-8175-9147
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Department of Pathology, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: So Dug
authors.identifier: 0000-0003-2036-0313
authors.initials: SD
authors.lastname: Lim
authors.affiliation: Department of Surgery, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Young-Bum
authors.identifier: 0000-0002-6910-5076
authors.initials: YB
authors.lastname: Yoo
authors.affiliation: Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul, Korea.
authors.forename: Chan-Hyun
authors.identifier: 0000-0002-5711-2842
authors.initials: CH
authors.lastname: Na
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000032:analysis*; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D020543:Proteome / Q000032:analysis; D040901:Proteomics; D015203:Reproducibility of Results; D012269:Ribosomal Proteins / Q000032:analysis / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D010750:Phosphoproteins; D020543:Proteome; D012269:Ribosomal Proteins; C031937:phosphoprotein P2, ribosomal
keywords: Neoplasms; Pathology; Proteins; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thyroid Gland