Quantitative proteomic analysis of microdissected oral epithelium for cancer biomarker discovery

被引:40
作者
Xiao, Hua [1 ]
Langerman, Alexander [4 ]
Zhang, Yan [2 ]
Khalid, Omar [3 ]
Hu, Shen [3 ]
Cao, Cheng-Xi [1 ]
Lingen, Mark W. [4 ]
Wong, David T. W. [3 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Lab Bioseparat & Analyt Biochem, State Key Lab Microbial Metab, Shanghai 200240, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China
[3] Univ Calif Los Angeles, Sch Dent, Dent Res Inst, Los Angeles, CA 90095 USA
[4] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
基金
中国国家自然科学基金;
关键词
Oral epithelium; Laser capture microdissection; Quantitative proteomics; Tissue microarray; Biomarkers; SQUAMOUS-CELL CARCINOMA; ANNEXIN A1; EXPRESSION; HEAD; IDENTIFICATION; INFLAMMATION; MARKERS; PROTEIN; S100A8; RISK;
D O I
10.1016/j.oraloncology.2015.08.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1011 / 1019
页数:9
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