title: Quantitative proteomic analysis of microdissected oral epithelium for cancer biomarker discovery.
abstract: Specific biomarkers are urgently needed for the detection and progression of oral cancer. The objective of this study was to discover cancer biomarkers from oral epithelium through utilizing high throughput quantitative proteomics approaches. Morphologically malignant, epithelial dysplasia, and adjacent normal epithelial tissues were laser capture microdissected (LCM) from 19 patients and used for proteomics analysis. Total proteins from each group were extracted, digested and then labelled with corresponding isobaric tags for relative and absolute quantitation (iTRAQ). Labelled peptides from each sample were combined and analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) for protein identification and quantification. In total, 500 proteins were identified and 425 of them were quantified. When compared with adjacent normal oral epithelium, 17 and 15 proteins were consistently up-regulated or down-regulated in malignant and epithelial dysplasia, respectively. Half of these candidate biomarkers were discovered for oral cancer for the first time. Cornulin was initially confirmed in tissue protein extracts and was further validated in tissue microarray. Its presence in the saliva of oral cancer patients was also explored. Myoglobin and S100A8 were pre-validated by tissue microarray. These data demonstrated that the proteomic biomarkers discovered through this strategy are potential targets for oral cancer detection and salivary diagnostics.
authors: State Key Laboratory of Microbial Metabolism, Laboratory of Bioseparation and Analytical Biochemistry, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: huaxiao@sjtu.edu.cn.
authors: Hua
authors: H
authors: Xiao
authors: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors: Alexander
authors: A
authors: Langerman
authors: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors: Yan
authors: Y
authors: Zhang
authors: Dental Research Institute, School of Dentistry, University of California-Los Angeles, Los Angeles, CA 90095, USA.
authors: Omar
authors: O
authors: Khalid
authors: Dental Research Institute, School of Dentistry, University of California-Los Angeles, Los Angeles, CA 90095, USA.
authors: Shen
authors: S
authors: Hu
authors: State Key Laboratory of Microbial Metabolism, Laboratory of Bioseparation and Analytical Biochemistry, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors: Cheng-Xi
authors: CX
authors: Cao
authors: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors: Mark W
authors: MW
authors: Lingen
authors: Dental Research Institute, School of Dentistry, University of California-Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dtww@ucla.edu.
authors: David T W
authors: DTW
authors: Wong
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002853:Chromatography, Liquid; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D009055:Mouth / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarkers; Laser capture microdissection; Oral epithelium; Quantitative proteomics; Tissue microarray