The ability to diagnose cancer at an early stage will greatly enhance chances of treatment success and reduce the mortality and morbidity. Currently there is no molecular test that can diagnose or screen for oral cancer non-invasively. We were able to identify a 7-gene signature that can predict the presence of an oral cancer with an accuracy of 82%. Since 2004, the characterization and diagnostic use of human salivary RNA has been actively pursued in our laboratory. Our proposal, """"""""Collection, Stabilization and Storage of Saliva Samples for Cancer Research,"""""""" responds to the RFA titled """"""""Innovations in Cancer Sample Preparation"""""""" (RFA CA-07-037). We will develop optimal and standardized collection, RNA stabilization, storage and processing protocols to perform gene expression analysis of salivary mRNA. We propose three Specific Aims to address the multifaceted nature of this RFA.
Aim 1 will establish optimal extraction methods for mRNA from saliva.
In Aim 2 we will determine the intra-individual fluctuation of mRNA levels, define adequate endogenous transcripts for normalization and validate our oral cancer markers and additional new candidates in an independent cohort.
In Aim 3 we will determine stability of saliva and expression patterns over periods of up to 6 months with different storage conditions and with stabilizing reagent. In all aims we will apply a new method for the multiplex reverse transcription and pre-amplification with subsequent quantitative PCR of a variety of mRNA transcripts endogenous to saliva. In addition, our set-up allows the implementation of several spike sequences that will yield important insights in the extraction and storage and are ideal controls for clinical application. We are confident that our research can be translated directly into a study for the large validation of oral cancer markers and spark the initiation of a multitude of projects and sample collections for the use of saliva as a diagnostic tool for oral and systemic diseases. Our studies will contribute to the advancement of human saliva as a clinically important body fluid for molecular diagnosis to improve cancer-directed health care. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA126733-01A1
Application #
7434301
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (J1))
Program Officer
Krueger, Karl E
Project Start
2008-04-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
1
Fiscal Year
2008
Total Cost
$207,900
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; Lin, Chien-Chung et al. (2016) The emerging landscape of salivary diagnostics. Periodontol 2000 70:38-52
Chiang, Samantha H; Thomas, Gerald A; Liao, Wei et al. (2015) RNAPro•SAL: a device for rapid and standardized collection of saliva RNA and proteins. Biotechniques 58:69-76
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
Fuentes, L; Yakob, M; Wong, D T W (2014) Emerging horizons of salivary diagnostics for periodontal disease. Br Dent J 217:567-73
Farrell, James J; Zhang, Lei; Zhou, Hui et al. (2012) Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut 61:582-8
Elashoff, David; Zhou, Hui; Reiss, Jean et al. (2012) Prevalidation of salivary biomarkers for oral cancer detection. Cancer Epidemiol Biomarkers Prev 21:664-72
Xiao, Hua; Zhang, Lei; Zhou, Hui et al. (2012) Proteomic analysis of human saliva from lung cancer patients using two-dimensional difference gel electrophoresis and mass spectrometry. Mol Cell Proteomics 11:M111.012112
Baum, B J; Yates 3rd, J R; Srivastava, S et al. (2011) Scientific frontiers: emerging technologies for salivary diagnostics. Adv Dent Res 23:360-8
Zhang, Lei; Xiao, Hua; Karlan, Scott et al. (2010) Discovery and preclinical validation of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. PLoS One 5:e15573

Showing the most recent 10 out of 14 publications