Integrative Analysis Reveals Comprehensive Altered Metabolic Genes Linking with Tumor Epigenetics Modification in Pan-Cancer.

Background: Cancer cells undergo various rewiring of metabolism and dysfunction of epigenetic modification to support their biosynthetic needs. Although the major features of metabolic reprogramming have been elucidated, the global metabolic genes linking epigenetics were overlooked in pan-cancer.

Objectives: Identifying the critical metabolic signatures with differential expressions which contributes to the epigenetic alternations across cancer types is an urgent issue for providing the potential targets for cancer therapy.

Method: The differential gene expression and DNA methylation were analyzed by using the 5726 samples data from the Cancer Genome Atlas (TCGA).

Results: Firstly, we analyzed the differential expression of metabolic genes and found that cancer underwent overall metabolism reprogramming, which exhibited a similar expression trend with the data from the Gene Expression Omnibus (GEO) database. Secondly, the regulatory network of histone acetylation and DNA methylation according to altered expression of metabolism genes was summarized in our results. Then, the survival analysis showed that high expression of had a poorer overall survival in 5 cancer types. Integrative altered methylation and expression revealed specific genes influenced by through DNA methylation across cancers. These genes do not overlap across various cancer types and are involved in different function annotations depending on the tissues, which indicated might influence DNA methylation in tissue specificity.

Conclusions: Our research clarifies some key metabolic genes, , , , and , which are most disordered and indirectly contribute to the dysfunction of histone acetylation and DNA methylation in cancer. We also found some potential genes in different cancer types influenced by . Our study highlights possible epigenetic disorders resulting from the deregulation of metabolic genes in pan-cancer and provides potential therapy in the clinical treatment of human cancer.