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Title: Metabolomic Biomarkers for Colorectal Cancer
Author: Farshidfar, Farshad
Advisor: Bathe, Oliver F.
Keywords: Biostatistics;Biology--Molecular;Oncology;Biochemistry
Abstract: Colorectal cancer (CRC) is the second most common cancer in the North America. It is also a huge burden for society. Remarkable efforts have been and are being made to improve CRC diagnosis, to enhance the effectiveness of treatments, and to eventually improve the outcome of these patients. Metabolomic profiling, as a method for describing metabolic state and alterations in the molecular constituents and capable of yielding unique and invaluable information about tumor biology, has been employed. Using a range of spectroscopy and mass spectrometry techniques, we have sought to characterize the changes in the serum metabolome that appear as a result of malignant and pre-malignant lesions in the colon and rectum. In Chapter 2, Application of gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy for staging CRC is described. Chapter 3 describes a larger study of 320 CRC and 31 colorectal adenoma cases as well as their matching controls by GC-MS, which led to the identification of validated metabolomic signature for identification of CRC and a proposed signature for identification of colorectal adenoma. In chapter 4, an effort for quantitative profiling of 62 CRC cases and 31 colorectal adenomas and their matching controls by tandem mass spectrometry is illustrated, and a validated quantitative signature for diagnosis of CRC is reported. Chapter 5 is dedicated to studying the prognostic value of metabolomic profiling in colorectal liver metastatic patients, and a novel workflow for estimation of recurrence risk using high-dimensional data is proposed. Challenges and pitfalls confronted in different steps of the project were addressed when possible by the use of available methods. Where no reliable method was available, we made an effort to develop one. This thesis, therefore, is focused on the metabolomic characterization of CRC and the adaptation of this knowledge for the development of clinically valuable biomarkers.
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