NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in patients with colorectal cancer

Abstract

// Yan Lin 1 , Changchun Ma 2 , Chengkang Liu 1 , Zhening Wang 1 , Jurong Yang 3 , Xinmu Liu 4 , Zhiwei Shen 1 , Renhua Wu 1 1 Radiology Department, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong, China 2 Radiation Oncology, Affiliated Tumor Hospital, Shantou University Medical College, Shantou 515041, Guangdong, China 3 Shantou University, Central Laboratory and NMR Unit, Shantou 515041, Guangdong, China 4 Surgery Deparment, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong, China Correspondence to: Renhua Wu, email: rhwu@stu.edu.cn Keywords: colorectal cancer, 1 H NMR spectroscopy, metabolomics, fecal profile, OPLS-DA Received: December 01, 2015 Accepted: March 14, 2016 Published: April 16, 2016 ABSTRACT Colorectal cancer (CRC) is a growing cause of mortality in developing countries, warranting investigation into its earlier detection for optimal disease management. A metabolomics based approach provides potential for noninvasive identification of biomarkers of colorectal carcinogenesis, as well as dissection of molecular pathways of pathophysiological conditions. Here, proton nuclear magnetic resonance spectroscopy ( 1 HNMR) -based metabolomic approach was used to profile fecal metabolites of 68 CRC patients (stage I/II=20; stage III=25 and stage IV=23) and 32 healthy controls (HC). Pattern recognition through principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied on 1 H-NMR processed data for dimension reduction. OPLS-DA revealed that each stage of CRC could be clearly distinguished from HC based on their metabolomic profiles. Successive analyses identified distinct disturbances to fecal metabolites of CRC patients at various stages, compared with those in cancer free controls, including reduced levels of acetate, butyrate, propionate, glucose, glutamine, and elevated quantities of succinate, proline, alanine, dimethylglycine, valine, glutamate, leucine, isoleucine and lactate. These altered fecal metabolites potentially involved in the disruption of normal bacterial ecology, malabsorption of nutrients, increased glycolysis and glutaminolysis. Our findings revealed that the fecal metabolic profiles of healthy controls can be distinguished from CRC patients, even in the early stage (stage I/II), highlighting the potential utility of NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in CRC patients.