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Background  CpG island methylator phenotype (CIMP) is found in 15–20% of malignant colorectal tumors and is characterized by strong CpG hypermethylation over the genome. The molecular mechanisms of this phenomenon are not still fully understood. The development of CIMP is followed by global gene expression alterations and metabolic changes. In particular, CIMP-low colon adenocarcinoma (COAD), predominantly corresponded to consensus molecular subtype 3 (CMS3, “Metabolic”) subgroup according to COAD molecular classification, is associated with elevated expression of genes participating in metabolic pathways.    Methods  We performed bioinformatics analysis of RNA-Seq data from The Cancer Genome Atlas (TCGA) project for CIMP-high and non-CIMP COAD samples with DESeq2, clusterProfiler, and topGO R packages. Obtained results were validated on a set of fourteen COAD samples with matched morphologically normal tissues using quantitative PCR (qPCR).    Results  Upregulation of multiple genes involved in glycolysis and related processes ( ENO2, PFKP, HK3, PKM, ENO1, HK2, PGAM1, GAPDH, ALDOA, GPI, TPI1,  and  HK1 ) was revealed in CIMP-high tumors compared to non-CIMP ones. Most remarkably, the expression of the  PKLR  gene, encoding for pyruvate kinase participating in gluconeogenesis, was decreased approximately 20-fold. Up to 8-fold decrease in the expression of  OGDHL  gene involved in tricarboxylic acid (TCA) cycle was observed in CIMP-high tumors. Using qPCR, we confirmed the increase (4-fold) in the  ENO2  expression and decrease (2-fold) in the  OGDHL  mRNA level on a set of COAD samples.    Conclusions  We demonstrated the association between CIMP-high status and the energy metabolism changes at the transcriptomic level in colorectal adenocarcinoma against the background of immune pathway activation. Differential methylation of at least nine CpG sites in  OGDHL  promoter region as well as decreased  OGDHL  mRNA level can potentially serve as an additional biomarker of the CIMP-high status in COAD.    Electronic supplementary material  The online version of this article (10.1186/s12881-019-0771-5) contains supplementary material, which is available to authorized users.

The CIMP-high phenotype is associated with energy metabolism alterations in colon adenocarcinoma