Fig. 2
A Hierarchical clustering analysis of metabolite abundances from colorectum tissue samples. Abundances for metabolites significantly differentiating in at least one pairwise comparison between colorectum subsites are shown across seven colorectum subsites in tumors (39 metabolites). Abundances were averaged from each subsite. Metabolites highlighted with blue asterisk (19 metabolites) were commonly altered in both normal and tumor tissues. B Hierarchical clustering analysis of metabolite abundances from colorectum tissue samples. Abundances for metabolites significantly differentiating in at least one pairwise comparison between three major regions are shown across the left side colon, right side colon, and rectum in tumors. Abundances were averaged from each subsite. Metabolites highlighted with blue asterisk (25 metabolites) were commonly altered in both normal and tumor tissues. C Distribution of metabolite abundances showing concentration gradient exist from cecum to rectum in both tumors and normal mucosa. Linear regression analysis was performed between metabolite abundances and seven subsites. Three representative metabolites showing significantly linear trend (Plinear<0.05) from cecum to rectum. The concentration gradient is similar in both normal colon and colon tumor (glycoursodeoxycholic acid), concentration gradient is different between normal colon and colon tumor (N-acetylneuraminic acid and adenosine diphosphate). Each subsite is presented in a unique color. Red-Cecum, green-Ascending, blue-Transverse, cyan- Descending, light violet-Sigmoid, yellow-Rectosigmoid and dark violet-Rectum. D Subsite specific unique metabolites markers significantly (p < 0.05) associated with CRC prognosis. Hazard ratio (HR) for each metabolite (log2-transformed abundance) was calculated by Cox proportional hazard regression analysis between log2 abundances of individual metabolites and 5-year overall survival in each subsite, adjusting for age, sex, chemotherapy and stage. Error bars represent 95% confidence intervals (CIs). The unique survival metabolites for each subsite are color coded differently. Cecum-blue, Ascending-pink, Transverse-green, Descending-yellow, Sigmoid-purple, Rectosigmoid-grey, Rectum-ice blue. GDCA - Glycodeoxycholic acid, GUDCA -Glycoursodeoxycholic acid, 5-HIAA - 5-Hydroxyindole-3-acetic acid, N-acetylneuraminic acid, PAA - Phenylacetylglycine, PAGln - Phenylacetylglutamine, NMDA - N-Methyl-D-aspartic acid, E2-3G - Estradiol-3-glucuronide, gamma-Glu-Glu - Gamma-glutamylglutamate, g-Glu-epsilon-lys - Epsilon-(gamma-Glutamyl)lysine, SAM - S-Adenosyl-methionine, NAAG - N-Acetylaspartylglutamic acid