Serum Proteomic Approach for the Identification of Serum Biomarkers Contributed by Oral Squamous Cell Carcinoma and Host Tissue Microenvironment

被引:64
作者
Bijian, Krikor [1 ,2 ]
Mlynarek, Alex M. [1 ,2 ]
Balys, Richard L.
Jie, Su [1 ,2 ]
Xu, Yingjie [1 ,2 ]
Hier, Michael P. [1 ,2 ]
Black, Martin J. [1 ,2 ]
Di Falco, Marcos R. [3 ]
LaBoissiere, Sylvie [3 ]
Alaoui-Jamali, Moulay A. [1 ,2 ]
机构
[1] McGill Univ, Dept Oncol & Med, Lady Davis Inst Med Res, SMBD Jewish Gen Hosp, Montreal, PQ, Canada
[2] McGill Univ, Segal Comprehens Canc Ctr, SMBD Jewish Gen Hosp, Montreal, PQ, Canada
[3] McGill Univ & Genome Quebec Proteom Platform, Montreal, PQ, Canada
关键词
head and neck; oral squamous cell carcinoma; serum; proteomics; biomarkers; GROWTH-FACTOR RECEPTOR; TANDEM MASS-SPECTROMETRY; METASTATIC BREAST-CANCER; NECK-CANCER; GEL-ELECTROPHORESIS; GELSOLIN EXPRESSION; HEAD; PROTEINS; INVASION; DISCOVERY;
D O I
10.1021/pr800979e
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The lack of serum biomarkers for head and neck carcinoma limits early diagnosis, monitoring of advanced disease, and prediction of relapses in patients. We conducted a comprehensive proteomics study on serum from mice bearing orthotopic human oral squamous cell carcinomas (OSCC) with distinct invasive phenotypes. Matched established cell lines were transplanted orthotopically into tongues of RAG-2/gamma(c) mice and mouse serum was analyzed by 2-dimensional-differential gel electrophoresis(2D-DIGE)/liquid chromatography (LC)-MS/MS and by online 2D-LC-MS/MS of iTRAQ labeled samples. We identified several serum proteins as being differentially expressed between control and cancer-bearing mice and between noninvasive and invasive cancer (p < 0.05). Differentially expressed proteins of human origin included the epidermal growth factor receptor (EGFR), cytokeratins, G-protein coupled receptor 87, Rab11 GTPase, PDZ-domain containing proteins, and PEST-containing nuclear proteins. Identified proteins of mouse origin included clusterin, titin, vitronectin, vitamin D-binding protein, hemopexin, and kininogen I. The levels of serum and cell secreted EGFR were further validated to match proteomic data regarding the inverse correlation with the invasive phenotype. In summary, we report a comprehensive patient-based proteomics approach for the identification of potential serum biomarkers for OSCC using an orthotopic xenograft mouse model.
引用
收藏
页码:2173 / 2185
页数:13
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