Excluding skin cancers, prostate cancer is the most frequently diagnosed cancer in American men. The American Cancer Society
estimated 220,800 new prostate cancer cases would be diagnosed in 2015. Prostate cancer is also the second leading cause of
cancer-specific mortality at 27,540 deaths estimated in 2015. Of particular concern are the increased incidence, mortality, and aggressive
features of prostate cancer seen in African American men. These health disparities are not fully explained by non-biological factors such
as socioeconomics, access to care, or treatment. Prostate cancer presents a compelling case for the clinical usefulness of biomarkers. The
lack of an assured prostate cancer susceptibility gene necessitates other molecular markers are required for screening. Because of its
slow-growing nature, early prostate cancer is asymptomatic so biomarkers that accurately diagnose asymptomatic prostate cancer would be of
great value. Additionally, prognostic markers to discriminate indolent and aggressive disease would be highly prized. The racial
differences in prostate cancer also suggest that biomarkers could be particularly useful in heavily burdened populations such as African
American men. For a myriad of reasons, however, biomarker discovery has not been as fruitful as anticipated in the wake of advances in
high-throughput genomic and proteomic technologies. Pathway analysis has emerged as a strategy for identifying molecular changes in
prostate cancer and uncovering molecular targets for biomarkers and therapy. The thread uniting the studies presented herein is the
application of pathway analysis to human prostate cancer to identify altered mechanisms of prostate cancer tumors development and
progression. Study 1 used comprehensive genomic patient data obtained from The Cancer Genome Atlas to identify differentially expressed
genes and pathway signatures in prostate cancer. This analysis highlighted the strong association of the "TGF-β signaling" and "Ran
regulation of mitotic spindle formation" with prostate cancer and confirmed reported findings from microarray data that suggest "Actin
Cytoskeleton Regulation", "Cell Cycle", "MAPK Signaling", and "Calcium Signaling" are also altered in prostate cancer. Study 2
incorporated a similar methodological approach to study paired RC-77 human prostate cancer cell lines. This cell model is one of few
models derived from an African American patient. This work completed the first comprehensive proteomic analysis of RC-77 cell lines and
found 63 differentially expressed proteins between the malignant RC-77T/E cell line and the non-malignant RC-77N/E, with 18 proteins
uniquely detected in RC-77T/E and 2 proteins uniquely detected in RC-77N/E. Many of these differentially expressed proteins fall into the
category of structural proteins or have a structural role. A pathway approach was used to provide a context for these differences and
revealed correlation of the "Tight Junction", "Cell Adhesion Molecules", "Adherens Junction", "ECM-Receptor interaction", "Focal
Adhesion", and "Proteoglycans in Cancer" pathways with either RC-77T/E or RC-77N/E cells. Study 3 applied the pathway analysis to race-,
age-, and stage-matched malignant and non-malignant prostate tissues to examine pathway dysregulation in the context of racial health
disparities. While this small case study was not able to show racial differences in the expression of individual genes, pathways were
differentially associated with African American prostate cancer. Three supplementary files containing the expression data and full
analysis results for each project are included with this dissertation: Supplementary File 1 (MyersJS_SuppInfo_GenomicData_TCGA.xlsx),
Supplementary File 2 (MyersJS_SuppInfo_ProteomicData_RC77.xlsx), and Supplementary File 3
(MyersJS_SuppInfo_ProteomicData_Tissues.xlsx). / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of
the Doctor of Philosophy. / Spring Semester 2016. / March 28, 2016. / genomics, health disparity, pathway analysis, prostate cancer, proteomics / Includes bibliographical references. / Qing-Xiang Sang, Professor Directing Dissertation; Wu-Min Deng, University Representative; Alan
G. Marshall, Committee Member; Michael Roper, Committee Member; Michelle Arbeitman, Committee Member.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_360536 |
| Contributors | Myers, Jennifer Shonequa (authoraut), Sang, Qing-Xiang Amy (professor directing dissertation), Deng, Wu-Min (university representative), Marshall, Alan G. (Alan George) (committee member), Roper, Michael Gabriel (committee member), Arbeitman, Michelle N. (committee member), Florida State University (degree granting institution), College of Arts and Sciences (degree granting college), Department of Chemistry and Biochemistry (degree granting department) |
| Publisher | Florida State University, Florida State University |
| Source Sets | Florida State University |
| Language | English, English |
| Detected Language | English |
| Type | Text, text |
| Format | 1 online resource (253 pages), computer, application/pdf |
| Rights | This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them. |
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