ArticleBMC medical genetics2019
The CIMP-high phenotype is associated with energy metabolism alterations in colon adenocarcinoma.
Article in BMC medical genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 31 citations in OpenAlex.
- Hypermethylated Colorectal Cancer Tumours Present a Myc-Driven Hypermetabolism with a One-Carbon Signature Associated with Worsen Prognosis.Biomedicines · 2024Article
- Metabolism-associated molecular classification of cervical cancer.BMC women's health · 2023Article
- An integrated model for predicting KRAS dependency.PLoS computational biology · 2023Article
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- Comprehensive analysis of the prognosis, tumor microenvironment, and immunotherapy response of SDHs in colon adenocarcinoma.Frontiers in immunology · 2023Article
- Epigenetically programmed resistance to chemo- and immuno-therapies.Advances in cancer research · 2023Article
- Article
- Metabolism-Associated Molecular Classification of Colorectal Cancer.Frontiers in oncology · 2020Article
- A model of twenty-three metabolic-related genes predicting overall survival for lung adenocarcinoma.PeerJ · 2020Article
- Editorial: Bioinformatics of Genome Regulation and Systems Biology.Frontiers in genetics · 2020Article
- Medical genetics studies at BGRS conference series.BMC medical genetics · 2019Article
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCpG 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.
methodsWe 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).
resultsUpregulation 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.
conclusionsWe 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.
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