Characterizing Oral Cancer Progression Via Saliva Proteomics
Timothy J Griffin
Biochemistry, Molecular Biology And Biophysics (bmuniversity Of Minnesota Twin Cities
450 Mcnamara Alumni Center
minneapolis, Mn 554552070
Grant 1R01DE017734-01A2 from National Institute Of Dental & Craniofacial Research IRG: EBT
Abstract: Oral cancer accounts for over 30,000 cases of cancer per year in the United States and is the sixth most common cancer worldwide. The five-year survival rate (approximately 50%) from these carcinomas is one of the worst for the major sites of cancer development, and has not significantly improved in the past 30 years. Reliable molecular markers that can predict this transition early in the process and be screened for in readily obtained clinical samples would enable more informed treatment and monitoring of patients, and help to significantly improve the prognosis of oral cancer patients. The overall objective of the proposed work is to address this critical need by identifying protein biomarkers in whole human saliva that are predictive of oral cancer development. This objective will be achieved through three Specific Aims 1) Characterize changes in the secreted saliva proteome associated with oral cancer progression; 2) Characterize changes in the exfoliated oral epithelial cellular proteome and tissue biopsies associated with oral cancer progression; 3) Validate candidate predictive oral cancer protein biomarkers via targeted mass spectrometric analysis. Strategies developed by the assembled research team, including novel peptide fractionation methods, targeted mass spectrometry-based biomarker validation methods, and enabling computational and bioinformatic tools will be employed. A highly informative oral cancer progression model will be analyzed, composed of unique clinical samples collected from individuals at intermediate stages of oral cancer development, controlling for the risk factor of smoking, and enabling the identification of diagnostic protein changes at the earliest stages of cancer development. Taken together, the combination of advanced technologies, availability of unique clinical samples, and the collective expertise of the assembled research team will provide for the successful discovery and validation of promising clinical biomarkers of oral cancer. RELEVANCE TO PUBLIC HEALTH The proposed studies will identify proteins in clinical saliva samples that are predictive of oral cancer development, providing promising diagnostic markers which can be developed into routine clinical patient tests. As such the findings from the proposed studies will have a direct impact on improving the diagnosis and treatment of oral cancer in the clinic, thereby leading to a decrease in the significant suffering and death caused by this cancer
Project start date: 2007-08-01
Project end date: 2011-06-30
1R01DE017734-01A2 (2007): $358517
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Timothy J Griffin
CHARACTERIZING ORAL CANCER PROGRESSION VIA SALIVA PROTEOMICS
Timothy J Griffin
University Of Minnesota Twin Cities, 450 Mcnamara Alumni Center, Minneapolis, Mn 55455-2070
Grant 5R01DE017734-04 from National Institute Of Dental & Craniofacial Research
Abstract: Oral cancer accounts for over 30,000 cases of cancer per year in the United States and is the sixth most common cancer worldwide. The five-year survival rate (approximately 50%) from these carcinomas is one of the worst for the major sites of cancer development, and has not significantly improved in the past 30 years. Reliable molecular markers that can predict this transition early in the process and be screened for in readily obtained clinical samples would enable more informed treatment and monitoring of patients, and help to significantly improve the prognosis of oral cancer patients. The overall objective of the proposed work is to address this critical need by identifying protein biomarkers in whole human saliva that are predictive of oral cancer development. This objective will be achieved through three Specific Aims 1) Characterize changes in the secreted saliva proteome associated with oral cancer progression; 2) Characterize changes in the exfoliated oral epithelial cellular proteome and tissue biopsies associated with oral cancer progression; 3) Validate candidate predictive oral cancer protein biomarkers via targeted mass spectrometric analysis. Strategies developed by the assembled research team, including novel peptide fractionation methods, targeted mass spectrometry-based biomarker validation methods, and enabling computational and bioinformatic tools will be employed. A highly informative oral cancer progression model will be analyzed, composed of unique clinical samples collected from individuals at intermediate stages of oral cancer development, controlling for the risk factor of smoking, and enabling the identification of diagnostic protein changes at the earliest stages of cancer development. Taken together, the combination of advanced technologies, availability of unique clinical samples, and the collective expertise of the assembled research team will provide for the successful discovery and validation of promising clinical biomarkers of oral cancer. RELEVANCE TO PUBLIC HEALTH The proposed studies will identify proteins in clinical saliva samples that are predictive of oral cancer development, providing promising diagnostic markers which can be developed into routine clinical patient tests. As such the findings from the proposed studies will have a direct impact on improving the diagnosis and treatment of oral cancer in the clinic, thereby leading to a decrease in the significant suffering and death caused by this cancer
Keywords: Accounting; Address; Analysis, Data; Analytical Chemistry; Area; Articulation; Award; Bio-Informatics; Bioinformatics; Biological; Biopsy; Body Tissues; Cancer Cause; Cancer Diagnostics; Cancer Etiology; Cancer Patient; Cancer Staging; Cancers; Carcinoma; Cations; Cause of Death; Chemical Fractionation; Chemistry; Chemistry, Analytic; Chemistry, Analytical; Clinic; Clinical; Collaborations; Complement; Complement Proteins; Complex; Contracting Opportunities; Contracts; Coupled; Data; Data Analyses; Data Set; Dataset; Detection; Development; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Diagnostic tests; Early Diagnosis; Effectiveness; Ensure; Environment; Epithelial; Epithelial Neoplasms, Malignant; Epithelial Tumors, Malignant; FRACN; Forecast of outcome; Fractionation; Fractionation Radiotherapy; Funding; Goals; Head and Neck, Saliva; Human; Human, General; Hybrids; Individual; Investigators; Joints; Label; Liquid substance; Malignant Neoplasms; Malignant Oral Cavity Neoplasm; Malignant Oral Cavity Tumor; Malignant Oral Neoplasm; Malignant Tumor; Malignant Tumor of the Mouth; Malignant neoplasm of mouth; Man (Taxonomy); Man, Modern; Mass Spectrum; Mass Spectrum Analysis; Methods; Modeling; Mouth Cancer; Names; Neoplasm Staging; Oral; Oral Cancer; Oral Cavity Squamous Cell Carcinoma; Oral squamous cell carcinoma; Paper; Patient Monitoring; Patients; Peptides; Phase; Photometry/Spectrum Analysis, Mass; Position; Positioning Attribute; Postdoc; Postdoctoral Fellow; Pre-Malignant; Premalignant; Probability; Process; Prognosis; Programs (PT); Programs [Publication Type]; Proteins; Proteome; Proteomics; Public Health; Publishing; Reagent; Research; Research Associate; Research Personnel; Researchers; Risk Factors; SCC of the Mouth; SCC of the Oral Cavity; Saliva; Salivary; Sampling; Science of Chemistry; Screening for Oral Cancer; Screening procedure; Smoking; Spectrometry, Mass; Spectroscopy, Mass; Spectrum Analyses, Mass; Spectrum Analysis, Mass; Squamous cell carcinoma of mouth; Staging; Survival Rate; Technology; Testing; Time; Tissue Sample; Tissues; Training; Translational Research; Translational Research Enterprise; Translational Science; Translations; Tumor Staging; United States; Update; Validation; Work; base; biomarker; cancer chemoprevention; cancer location; cancer progression; cancer site; candidate validation; clinical Diagnosis; clinical practice; early detection; epithelial carcinoma; fluid; gene product; graduate student; improved; liquid; malignancy; malignant mouth neoplasm; molecular marker; mouth lesion; mouth squamous cell carcinoma; neoplasm progression; neoplasm/cancer; neoplastic progression; novel; oral cancer early detection; oral lesion; oral squamous carcinoma; outcome forecast; post-doc; post-doctoral; precancerous; programs; public health medicine (field); saliva proteome; saliva proteomic analysis; saliva proteomics; screening; screenings; success; tandem mass spectrometry; tool; translation research enterprise; tumor; tumor progression
Project start date: 2007-08-01
Project end date: 2011-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
5R01DE017734-04 (2010): $350755
5R01DE017734-03 (2009): $354392
5R01DE017734-02 (2008): $354484