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Quantitative Proteomics of Oral Precancer Progression

Institution: University of California, Los Angeles
Investigator(s): Shen Hu, Ph.D.
Award Cycle: 2009 (Cycle 18) Grant #: 18XT-0114 Award: $249,605
Subject Area: Cancer
Award Type: Exploratory/Developmental Award
Abstracts

Initial Award Abstract
Oral cancer, predominantly oral squamous cell carcinoma (OSCC), is a deadly disease affecting over 300,000 people worldwide annually. OSCC occurs twice as often in the black population as in whites. Racial disparities also exist in 5-year relative survival rates, with whites having the highest rates and black males the lowest rates. Despite the high morbidity rate of human oral cancer, the molecular events leading to the progression of oral precancer to cancer are still elusive. Currently there is no molecular and clinical parameter that can predict the malignant progression of oral precancers. This proposal aims to determine the quantitative changes in protein expression that are associated with oral precancer progression using emerging proteomic technologies. First we will demonstrate a new proteomics approach for studying oral cancer. This approach is based on quantitative analysis of microdissected FFPE (formalin-fixed paraffin-embedded) tissues using stable isotope labeling (iTRAQ) and monolithic liquid chromatography-tandem mass spectrometry (Aim 1). Next, we will apply the established methodology to analysis of oral premalignancies in vivo. Quantitative proteomic analysis of progressing and non-progressing oral cancers from minority, under-researched patient populations will be performed to identify protein biomarkers for oral precancer progression (Aim 2). The hypothesis to be tested is that there are distinct protein alterations between progressing and nonprogressing oral precancers, which may predict the malignancy-converting potential of oral precancer lesions. Discovery of the proteomic biomarkers for oral precancer progression can be translate into prediction models for early disease detection and may contribute to understanding the molecular mechanism of oral carcinogenesis. Ultimately we aim to understand the synergistic role and related signal pathways of the discovered targets in oral carcinogenesis. Since our study design is specifically targeted at the under-researched patient populations, the research findings may facilitate the early detection/screening of oral cancer in these populations and therefore contribute to reducing racial disparities in oral cancer morbidity and mortality.
Publications

Oral lichen planus is a unique disease model for studying chronic_x000d_ inflammation and oral cancer
Periodical: Medical Hypotheses Index Medicus:
Authors: Liu Y, Messadi DV, Wu H, Hu S. ART
Yr: 2010 Vol: 75 Nbr: 6 Abs: Pg: 492-4