Tumor metastasis is the dominant cause of death in cancer patients, including oral tongue squamous cell carcinoma (SCC) patients. The presence of lymph node metastasis in the neck is an important prognostic factor and crucial in making clinical decisions regarding postoperative treatments and follow ups. However, the current clinical diagnosis of lymph node metastasis for early stage (T1-T2) oral tongue cancer is not ideal. Occult nodal metastasis can be expected in over 30% of patients with T1 and T2 tongue cancers and clinically metastasis negative (N0) necks. It is critically important to identify those cancers with metastasis potential for more aggressive therapy. The identification of molecular markers associated with the metastasis and the development of a prediction model based on these markers will improve clinical treatment decisions in the management of this dreadful cancer and would help to facilitate the development of therapeutic interventions for oral tongue SCC patients. This proposal aims to test the hypothesis that signature genomic and expressional alternations exist in oral tongue cancer that distinguish tumors that metastasize from those that do not. Patient resources are in place to permit genomic and expressional studies including early stage (T1-T2) oral tongue cancer patients with known metastasis outcome (Aim 1). Bioinformatics and biocomputational expertise are in place to harness diagnostic molecular determinants in the metastatic oral tongue cancers and to build molecular classification model for tongue cancer metastasis (CMTCM) (Aim 2).
Aim 3 is to test the classification models in a multi-center setting to evaluate the clinical utility of this classification/prediction models for oral tongue cancer metastasis. The overarching aim of the proposal is to translate genome-wide discoveries into a predictive model that can forecast metastatic potential of early stage oral tongue SCC, and thus improve clinical treatment decisions in the management of oral tongue cancer. Relevance to Public Health (Project Narrative): This research project will lead to the discovery of biomarkers that can be used for the detection of oral tongue cancer metastasis, which will improve the management and treatment of oral tongue cancer patients. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA139596-01A2
Application #
7384024
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Jessup, John M
Project Start
2008-09-08
Project End
2013-07-31
Budget Start
2008-09-08
Budget End
2009-07-31
Support Year
1
Fiscal Year
2008
Total Cost
$408,434
Indirect Cost
Name
University of California Los Angeles
Department
Dentistry
Type
Schools of Dentistry
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Modi, Ashwin; Morou-Bermudez, Evangelia; Vergara, Jose et al. (2017) Validation of two point-of-care tests against standard lab measures of NO in saliva and in serum. Nitric Oxide 64:16-21
Zhang, Yong; Sun, Jie; Li, Feng et al. (2017) Salivary extracellular RNA biomarkers for insulin resistance detection in hispanics. Diabetes Res Clin Pract 132:85-94
Wang, Wei; He, Qianting; Yan, Wangxiang et al. (2017) High glucose enhances the metastatic potential of tongue squamous cell carcinoma via the PKM2 pathway. Oncotarget 8:111770-111779
He, Qianting; Chen, Zujian; Cabay, Robert J et al. (2016) microRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection. Oral Oncol 57:15-20
Zhao, Tingting; He, Qianting; Liu, Zhonghua et al. (2016) Angiotensin II type 2 receptor-interacting protein 3a suppresses proliferation, migration and invasion in tongue squamous cell carcinoma via the extracellular signal-regulated kinase-Snai2 pathway. Oncol Lett 11:340-344
He, Qianting; Chen, Zujian; Dong, Qian et al. (2016) MicroRNA-21 regulates prostaglandin E2 signaling pathway by targeting 15-hydroxyprostaglandin dehydrogenase in tongue squamous cell carcinoma. BMC Cancer 16:685
Zhang, Yong; Sun, Jie; Lin, Chien-Chung et al. (2016) The emerging landscape of salivary diagnostics. Periodontol 2000 70:38-52
Wong, David T W (2015) Salivary extracellular noncoding RNA: emerging biomarkers for molecular diagnostics. Clin Ther 37:540-51
Yakob, Maha; Fuentes, Laurel; Wang, Marilene B et al. (2014) Salivary biomarkers for detection of oral squamous cell carcinoma - current state and recent advances. Curr Oral Health Rep 1:133-141
Chen, Dan; Chen, Zujian; Jin, Yi et al. (2013) MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells. PLoS One 8:e80625

Showing the most recent 10 out of 36 publications