Unsurprisingly, many of the 20 most significantly associated pathways are related to immunological functions (tables 3, 4), with the most significantly associated pathway in both analyses being the glucocorticoid receptor signalling pathway.
Mirzaei M, Gupta VB, Chick JM, Greco TM, Wu Y, Chitranshi N, et al. Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes.
Interestingly, the PI3K-AKT-activation pathway (35 genes from the reactome gene-set) was recently shown to be among the most strongly associated pathways for ICV in an enrichment analysis testing 671 Reactome gene-sets using the same cohorts42.
Another possible cell death associated pathway resulting in activation of ATF3 by TRD is the ER stress response pathway [ 55, 56], since TRD has been reported to inhibit protein translation in tumour cells at an early stage [ 37].
Furthermore, global DNA hypomethylation and CIMP are possibly inversely associated in CRC [ 41], and methyl group donors may have an effect on both of these potentially distinct methylation-associated pathways in colorectal carcinogenesis.
