EPIGENOMIC VARIABILITY AND TRANSCRIPTOMICS AS A NOVEL MULTIOMIC COMPLEMENTARY APPROACH FOR PERSONALIZED NUTRITION IN COLORECTAL CANCER PATIENTS

Abstract

Food natural compounds are of interest as modulators of cancer progression and prognosis, as they participate in cellular processes such as growth and differentiation, DNA repair, programmed cell death and oxidative stress. Here we select dietary biocompounds for specific subgroups of 285 colorectal adenocarcinoma (COAD) samples by finding bioactives with opposite transcriptomic profiles to the subgroup-specific tumoral transcriptomes, hypothesizing they may counteract the cancer gene-expression profiles. To establish a CRC classification based on epigenetic variability, we selected 2,189 CpGs based on their differentially variable methylation between tumor and normal samples by a combination of linear and Bartlett tests. Samples were meta-clustered by 1) classifying each sample by 8 different methods (including k-means and hierarchical clustering), 2) building a network and 3) meta-clustering it by the edge-betweenness method. We extracted 6 main subgroups, 2 of them with immune-affected transcriptomes. We compared the transcriptomes of the 6 subgroups with the ones of 56 in vitro bioactive studies from GEO by Gene Set Enrichment Analysis (GSEA), resulting in a potential positive effect of resveratrol, japonicone A and vitamin D. In summary, we present a promising in silico strategy to suggest specific bioactives as co-adjuvants in cancer treatment.