Serum proteomic approach for the identification of serum biomarkers contributed by oral squamous cell carcinoma and host tissue microenvironment.
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.
Bijian
Krikor
K
Department of Oncology and Medicine, Otolaryngology-Head and Neck Surgery, Lady Davis Institute for Medical Research and Segal Comprehensive Cancer Center, SMBD Jewish General Hospital, McGill University, Montreal, QC, Canada.
Mlynarek
Alex M
AM
Balys
Richard L
RL
Jie
Su
S
Xu
Yingjie
Y
Hier
Michael P
MP
Black
Martin J
MJ
Di Falco
Marcos R
MR
LaBoissiere
Sylvie
S
Alaoui-Jamali
Moulay A
MA
D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis* / Q000302:isolation & purification; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D002853:Chromatography, Liquid; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D066246:ErbB Receptors / Q000097:blood; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D009374:Neoplasms, Experimental / Q000097:blood / Q000378:metabolism / Q000473:pathology; D040901:Proteomics / Q000379:methods*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D001798:Blood Proteins; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D066246:ErbB Receptors