Exploring Metabolic Profile Differences between Colorectal Polyp Patients and Controls Using Seemingly Unrelated Regression.
Despite the fact that colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the world, the development of improved and robust biomarkers to enable screening, surveillance, and therapy monitoring of CRC continues to be evasive. In particular, patients with colon polyps are at higher risk of developing colon cancer; however, noninvasive methods to identify these patients suffer from poor performance. In consideration of the challenges involved in identifying metabolite biomarkers in individuals with high risk for colon cancer, we have investigated NMR-based metabolite profiling in combination with numerous demographic parameters to investigate the ability of serum metabolites to differentiate polyp patients from healthy subjects. We also investigated the effect of disease risk on different groups of biologically related metabolites. A powerful statistical approach, seemingly unrelated regression (SUR), was used to model the correlated levels of metabolites in the same biological group. The metabolites were found to be significantly affected by demographic covariates such as gender, BMI, BMI(2), and smoking status. After accounting for the effects of the confounding factors, we then investigated potential of metabolites from serum to differentiate patients with polyps and age matched healthy controls. Our results showed that while only valine was slightly associated, individually, with polyp patients, a number of biologically related groups of metabolites were significantly associated with polyps. These results may explain some of the challenges and promise a novel avenue for future metabolite profiling methodologies.
Chen
C
Chen
‡Department of Electronic Science and Communication Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, Fujian Province 361005, China.
Lingli
L
Deng
Siwei
S
Wei
∥Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington 98109, United States.
G A
GA
Nagana Gowda
∥Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington 98109, United States.
Haiwei
H
Gu
⊥Indiana University Melvin and Bren Simon Cancer Center, 535 Barnhill Drive, Indianapolis, Indiana 46202, United States.|#Department of Medicine, University of Washington, 825 Eastlake Avenue East, Seattle, Washington 98109, United States.
Elena G
EG
Chiorean
⊥Indiana University Melvin and Bren Simon Cancer Center, 535 Barnhill Drive, Indianapolis, Indiana 46202, United States.
Mohammad
M
Abu Zaid
Marietta L
ML
Harrison
Joseph F
JF
Pekny
⊥Indiana University Melvin and Bren Simon Cancer Center, 535 Barnhill Drive, Indianapolis, Indiana 46202, United States.
Patrick J
PJ
Loehrer
Dabao
D
Zhang
Min
M
Zhang
∥Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington 98109, United States.|△Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, United States.
Daniel
D
Raftery
D016022:Case-Control Studies; D003111:Colonic Polyps / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012002:Rectal Diseases / Q000378:metabolism* / Q000473:pathology
NMR spectroscopy; colorectal polyp; metabolic profiling; metabolomics; seemingly unrelated regression