Anti-FABP6 (aa 1-129) polyclonal antibody

BackgroundColorectal cancer (CRC) is a multifactorial disease resulting from both genetic predisposition and environmental factors including the gut microbiota (GM), but deciphering the influence of genetic variants, environmental variables, and interactions with the GM is exceedingly difficult. We previously observed significant differences in intestinal adenoma multiplicity between C57BL/6J-Apc(Min) (B6-Min/J) from The Jackson Laboratory (JAX), and original founder strain C57BL/6JD-Apc(Min) (B6-Min/D) from the University of Wisconsin.MethodsTo resolve genetic and environmental interactions and determine their contributions we utilized two genetically inbred, independently isolated Apc(Min) mouse colonies that have been separated for over 20 generations. Whole genome sequencing was used to identify genetic variants unique to the two substrains. To determine the influence of genetic variants and the impact of differences in the GM on phenotypic variability, we used complex microbiota targeted rederivation to generate two Apc mutant mouse colonies harboring complex GMs from two different sources (GMJAX originally from JAX or GMHSD originally from Envigo), creating four Apc(Min) groups. Untargeted metabolomics were used to characterize shifts in the fecal metabolite profile based on genetic variation and differences in the GM.ResultsWGS revealed several thousand high quality variants unique to the two substrains. No homozygous variants were present in coding regions, with the vast majority of variants residing in noncoding regions. Host genetic divergence between Min/J and Min/D and the complex GM additively determined differential adenoma susceptibility. Untargeted metabolomics revealed that both genetic lineage and the GM collectively determined the fecal metabolite profile, and that each differentially regulates bile acid (BA) metabolism. Metabolomics pathway analysis facilitated identification of a functionally relevant private noncoding variant associated with the bile acid transporter Fatty acid binding protein 6 (Fabp6). Expression studies demonstrated differential expression of Fabp6 between Min/J and Min/D, and the variant correlates with adenoma multiplicity in backcrossed mice.ConclusionsWe found that both genetic variation and differences in microbiota influences the quantitiative adenoma phenotype in Apc(Min) mice. These findings demonstrate how the use of metabolomics datasets can aid as a functional genomic tool, and furthermore illustrate the power of a multi-omics approach to dissect complex disease susceptibility of noncoding variants.

Objective: To screen the gene signature for distinguishing patients with high risks from those with low-risks for colon cancer recurrence and predicting their prognosis. Methods: Five microarray datasets of colon cancer samples were collected from Gene Expression Omnibus database and one was obtained from The Cancer Genome Atlas (TCGA). After preprocessing, data in GSE17537 were analyzed using the Linear Models for Microarray data (LIMMA) method to identify the differentially expressed genes (DEGs). The DEGs further underwent PPI network-based neighborhood scoring and support vector machine (SVM) analyses to screen the feature genes associated with recurrence and prognosis, which were then validated by four datasets GSE38832, GSE17538, GSE28814 and TCGA using SVM and Cox regression analyses. Results: A total of 1207 genes were identified as DEGs between recurrence and no-recurrence samples, including 726 downregulated and 481 upregulated genes. Using SVM analysis and five gene expression profile data confirmation, a 15-gene signature (HESS, ZNF417, GLRA2, OR8D2, HOXA7, FABP6, MUSK, HTR6, GRIP2, KLRK1, VEGFA, AKAPI2, RHEB, NCRNA00152 and PMEPAI) were identified as a predictor of recurrence risk and prognosis for colon cancer patients. Conclusion: Our identified 15-gene signature may be useful to classify colon cancer patients with different prognosis and some genes in this signature may represent new therapeutic targets. (C) 2016 Published by Elsevier B.V.