Serum metabolite profiling of familial adenomatous polyposis using ultra performance liquid chromatography and tandem mass spectrometry

Abstract

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited intestinal polyposis syndrome accounting for about 1% of colorectal cancers (CRC). Despite increasing researches on the molecular pathogenesis of CRC, we are still unclear about metabolic pathways and alterations probably involved in the development of CRC. To obtain new insights into the mechanisms underlying APC mutation and to elucidate the mechanisms of CRC development, we performed to identify the potential metabolites in FAP based on metabolomic strategy. Serum metabolites from FAP patients (n = 30) and healthy individuals (n = 34) were detected and qualified using Ultra Performance Liquid Chromatography and Tandem Mass Spectrometry (UPLC− MS/MS). 118 metabolites were identified with statistical tests of orthogonal partial least-squares-discriminant analysis (OPLS−DA), with the conditions of variable importance in projection (VIP) >1, p < 0.05 using the Mann−Whitney U test, and fold change (FC) ≥2 or ≤0.5. OPLS-DA model was useful for distinguishing FAP patients from healthy controls. Unique metabolic signatures were pooled in FAP patients covering tricarboxylic acid (TCA) cycle, amino acids metabolism, vitamin D, fatty acids metabolism, and bile acids (BAs) metabolism. Our results demonstrated that metabolites alterations in FAP can be helpful for further analysis of metabonomics induced by APC mutation, and these alterations might be involved in the progress of intestinal carcinogenesis.