Metabolite profiling of breast cancer and its association with obesity by gas chromatography- mass spectrometry

Leiddy Z Alvarado, Purdue University

Abstract

The rapidly growing discipline of metabolite profiling, in which a large number of low molecular weight metabolites from body fluids or tissues are detected in a single step, hold a promising future for the early detection, prognosis, preventive screenings, therapy, personalized medicine, and for understanding the pathogenesis of numerous diseases. Mass spectrometry-based metabolomics is shown to provide a comprehensive analysis of endogenous metabolites for defining significantly altered metabolic pathways as a result of pathophysiological development. The high sensitivity of metabolite profiles can provide the means to detect the early onset of various biological perturbations, making small molecule metabolites very attractive biomarkers for early disease detection. This thesis primarily describes our findings resulting from the metabolite profiling of breast cancer, and the metabolic associations between obesity and breast cancer risk. The first part introduces and describes the use of metabolomics in cancer research and the various methods in practice today. The second part of this thesis describes the development and application of global metabolic profiling methods to different biomarker discovery studies. Using a combination of NMR and GCxGC-MS methods, we developed a highly sensitive blood test capable of detecting relapse an average of 13 months before it is diagnosed clinically, thereby opening a new window of opportunity for patients and oncologists to improve upon current treatments. Furthermore, we applied a GC-MS based global metabolic profiling approach to examine obesity and its association with the risk of developing breast cancer. From this study we detected a panel of metabolite biomarkers for understanding obesity from a systems biology standpoint. The results suggest that obesity could lead to significant perturbances to several pathways such as amino acid metabolism and fatty acid metabolism. We were able to identify a number of metabolites that describe the pathophysiological differences between women in the normal weight and obese range, many of which are also prevalent in breast cancer patients. Importantly, the study indicates that a high fraction of obese women have an altered metabolic phenotype that puts them at high risk for developing breast cancer. We conclude this thesis with a GC-MS based metabolic profiling approach used to discriminate healthy control from benign and carcinogenic breast tumors from women using blood serum as the biological specimen. We identified several metabolites present at altered levels in serum from breast cancer patients that, when combined using multivariate statistical methods, may be useful in developing simple and non-invasive preventative breast cancer screenings in the future.

Degree

Ph.D.

Advisors

Raftery, Purdue University.

Subject Area

Analytical chemistry|Oncology

Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server
.

Share

COinS