A High Resolution Metabolomics Study of Prostate Cancer 公开

Abstract

Background: Although it has been the subject of a multitude of sustained research endeavors, prostate cancer continues to be a major cause of morbidity and mortality in men. Examination of the metabolic profiles of men with prostate cancer could contribute to the identification of novel biomarkers of prostate cancer, thereby enhancing public health interventions and clinical practices.

Study Design: Cases (n=113) and controls (n=258) were selected from an existing, community-based case-control study conducted in the Piedmont Triadarea of North Carolina. Cases were over 50 years old, spoke English, and were newly diagnosed with prostate cancer. Cases and controls were frequency matched by age and race.

Results: Metabolomics analysis yielded 17697 metabolites, and 4485 metabolites with a median coefficient of variation value > 30 remained for statistical analysis. Of these, 27 metabolites, including aspartic acid, were associated with the presence of prostate cancer compared to matched controls.

Conclusion: The metabolic pathway of aspartic acid is significantly disturbed in men with prostate cancer. This finding suggests that aspartic acid may play a role in the disease mechanisms of prostate cancer.

Table of Contents

Chapter I: Background..........................................................................................................1

1.1: Descriptive Epidemiology...............................................................................................1

1.2: Prostate Cancer Carcinogenesis......................................................................................2

1.3: Prostate Cancer: Clinical Overview and Pathogenesis.......................................................5

1.4: Risk Factors...................................................................................................................6

1.5: Metabolomics................................................................................................................7

1.6: The Role of Metabolomics in Biomarker Discovery............................................................10

Chapter II: Materials and Methodology...................................................................................11

2.1: Study Subjects................................................................................................................11

2.2: Data Collection...............................................................................................................12

2.3: Metabolomics.................................................................................................................12

2.4: Statistical Analysis..........................................................................................................13

Chapter III: Results................................................................................................................15

3.1: Baseline Characteristics...................................................................................................15

3.2: Metabolites Distinguishing Prostate Cancer Cases from Controls........................................15

3.3: Association of Aspartic Acid with Prostate Cancer Risk.......................................................16

3.4: Stratified Analyses by Potential Effect Modifying Factors....................................................16

Chapter IV: Discussion...........................................................................................................17

4.1: Biological Plausibility of Findings.....................................................................................17

4.2: Our Work and Available Evidence......................................................................................18

4.3: Strengths and Limitations.................................................................................................19

4.4: Public Health Implications................................................................................................19

4.5: Future Directions.............................................................................................................20

4.6: Conclusion.......................................................................................................................20

References..............................................................................................................................22

Tables....................................................................................................................................26

Figures and Figure Legends......................................................................................................29

About this Master's Thesis

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• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Rollins School of Public Health
Department	Epidemiology
Degree	MSPH
Submission	Master's Thesis
Language	English
Research Field	Biology, Bioinformatics Health Sciences, Public Health Health Sciences, Epidemiology
关键词	Aspartic Acid Metabolomics Prostate Cancer
Committee Chair / Thesis Advisor	Fedirko, Veronika , Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs

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