Oral cancer is the sixth most common cancer worldwide ahead of Hodgkin's
lymphoma, leukemia, brain, stomach, or ovarian cancers, with about 41,000 Americans
being diagnosed annually. More than 90% of oral cancers are oral Squamous cell
carcinomas (OSCC). While the overall 5-year survival rate is about 60%, the survival rate
when diagnosed early is higher than 80%. Currently the standard for diagnosis of OSCC
is early visual detection of a suspicious oral lesion followed by scalpel biopsy with
histology. However, the invasiveness, expense, and required expertise involved prevents
consistent application on at risk individuals. Chapter 1 discusses the methods that are
being investigated for sampling and discovering biomarkers of OSCC that address some
of these limitations. Protein biomarkers contained in samples collected non-invasively
and directly from at-risk oral premalignant lesions (OPML) would address current needs
in a uniquely targeted fashion.
Chapter 2 of this thesis describes work evaluating the potential of a novel method
using commercial PerioPaper absorbent strips for the collection of oral lesion exudate
fluid coupled with mass spectrometry based proteomics for OSCC biomarker discovery.
This research focuses on demonstrating the feasibility of using oral lesion exudates in
proteomic research, exploring the proteome of exudate samples, discriminating between
exudates collected from clinically different sources, with supplemental table 1 showing
which proteins distinguish healthy and OPML sources. Furthermore, to ensure that the
best possible marker candidates are selected given clinical sample availability, multiple
methods were explored enable and improve quantitative proteomic analysis of exudates
in chapter 3 (Identified proteins in supplemental files 2 and 3). Our label-free
quantitative proteomics strategy analyzed paired control and OPML exudates (figure 8),
identifying differentially abundant proteins between sample types. Next, we selected
several [exudate] differentially abundant proteins for testing in while saliva, comparing
their relative abundance levels in healthy, OPML and oral Squamous cell carcinoma
(OSCC) subjects. Two proteins, CK10 and A1AT, showed differences in saliva. Our
results provide a demonstration of the value of tissue exudate analysis for guiding
salivary biomarker discovery in oral cancer, as well as providing promising biomarker
candidates for future evaluation.
University of Minnesota Ph.D. dissertation. April 2013. Major: Biochemistry, Molecular Biology, and Biophysics. Advisor: Timothy Griffin. 1 computer file (PDF); ix, 94 p. + 3 supplementary spreadsheet files.
Kooren, Joel Allan.
Informing the Oral Squamous Cell Carcinoma Biomarker Search by Exudate Proteomics.
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