Fig. 1: In silico analysis of miR-27a expression in the TCGA-COAD dataset.

a Overview of the strategy used to identify dysregulated molecular mechanisms in high- or low-miR-27a expressing tumours. On the left, ranked CRC samples based on miR-27a expression; the 75th and 25th percentile rank of expression values were used to categorise high- or low-miR-27a expressing CRCs, respectively. In the middle, GSEA analysis of a total of 3,272 gene-sets (see methods) to select those significantly enriched in high-miR-27a (q value < 0.1; Benjiamini-Hochberg multiple test correction) or low-miR-27a CRCs (q value < 0.1). On the right, leading-edge analysis to identify overlapping core-genes in the various gene-sets found enriched in high/low miR-27a CRCs; genes overlapping in at least five gene-sets were considered. b Ingenuity pathway analysis (IPA) of canonical pathways overrepresented in high-miR-27a CRCs. Overlapping pathways are shown together with significance of overrepresentation (q value; Benjiamini-Hochberg multiple test correction) and number of molecules overlapping in different pathways (numbers close to lines). c Heatmap of median of scores (see methods) in high-miR-27a (N = 71) and low-miR-27a (N = 71) CRCs of metabolic pathways as per the legend, i.e.: Glyc glycolysis; Pyr. Ox. pyruvate oxidation; TCA tricarboxylic acid cycle; PPP pentose phosphate pathway; mTOR sign. mTOR signalling; AMPK sign. AMPK signalling; Gln lysis glutaminolysis; GSH synth. glutathione synthesis. Colour codes in the heatmap indicate: predicted pathway activation (Activ., red), predicted pathway inhibition (Inhib., blue), significance of scores (−Log p value; calculated by the Mann–Whitney U test) difference in high- vs. low-miR-27a CRCs (grey scale). d Scatterplot shows the distribution of log₂ transformed TCPA metabolic proteins abundance ratio from high/low miR-27a. The p value is calculated by the Mann–Whitney U test. e Mutational analysis of 30 recurrently mutated genes with available information in TCGA-COAD cohort (224 patients). Columns represent patients and are ordered according to miR-27a expression level (upper coloured bar). Rows represent the mutational profile of each of the 29 genes across patients. The type of mutation for each gene is colour-coded as per the legend (see below the diagram). Tumour stages are indicated in the upper part of the diagram by coloured bars. Asterisks indicate significantly mutated genes upon comparing high- vs low-miR-27a CRCs (LR test).