Access Type

Open Access Dissertation

Date of Award

January 2011

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Nutrition and Food Science

First Advisor

Smiti V. Gupta

Abstract

Lung cancer is the leading cause of cancer deaths in the US, in part due to poor diagnosis. Prognosis can be improved, if detected at an early stage. The objective of this study was to use the metabolomic approach to investigate early potential biomarkers for lung cancer. Golden Syrian hamsters were randomized into two groups (treatment and control). Lung cancer was induced in treatment group by a chemical carcinogen, N-nitrosobis-2-(oxopropyl) amine (BOP) while the control animals were injected with saline. Urine was collected weekly throughout the study and frozen at -800 C. Proton nuclear magnetic resonance (1H NMR) spectra, acquired using Varian 500 MHz magnet were processed using ACD labs software. The processed, digitized NMR spectral data was analyzed using multivariate data analysis software, SIMCA P+. Principal Component Analysis (PCA) score plots showed clear significant (p < 0.05) separation between the cancer and control groups. The metabolites responsible for the differences between the two groups as observed from the PCA loading plots were quantified using CHENOMX NMR metabolite database. The metabolites (n=26) found to be significantly different (p<0.05) in the two groups were traced back to their respective biochemical pathways in an effort to gain mechanistic insight into lung cancer progression from the metabolite view point. Some of these metabolites such as glycine, sarcosine , and alanine have been previously reported to be increased in other cancer types like prostate. These could potentially serve as potential biomarkers of cancer in general. In addition, some metabolites may be of specific relevance to progression of lung cancer and may therefore be further explored as possible biomarkers of this aggressive cancer type

Download

Included in

Nutrition Commons

Share

COinS