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Background:  Reprogramming of cell metabolism is one of the most important hallmarks of breast cancer. This study aimed to comprehensively analyze metabolic genes in the initiation, progression, and prognosis of breast cancer.   Materials and Methods:  Data from The Cancer Genome Atlas (TCGA) in breast cancer were downloaded including RNA-seq, copy number variation, mutation, and DNA methylation. A gene co-expression network was constructed by the weighted correlation network analysis (WGCNA) package in R. Association of metabolic genes with tumor-related immune cells and clinical parameters were also investigated.   Results:  We summarized 3,620 metabolic genes and observed mutations in 2,964 genes, of which the most frequently mutated were PIK3CA (51%), TNN (26%), and KMT2C (15%). Four genes (AKT1, ERBB2, KMT2C, and USP34) were associated with survival of breast cancer. Significant association was detected in the tumor mutation burden (TMB) of metabolic genes with T stage ( p  = 0.045) and N stage ( p  = 0.004). Copy number variations were significantly associated with recurrence and prognosis of breast cancer. The co-expression network for differentially expressed metabolic genes by WGCNA suggested that the modules were associated with glycerophospholipid, arachidonic acid, carbon, glycolysis/gluconeogenesis, and pyrimidine/purine metabolism. Glycerophospholipid metabolism correlated with most of the immune cells, while arachidonic acid metabolism demonstrated a significant correlation with endothelial cells. Methylation and miRNA jointly regulated 14 metabolic genes while mutation and methylation jointly regulated PIK3R1.   Conclusion:  Based on multi-omics data of somatic mutation, copy number variation, mRNA expression, miRNA expression, and DNA methylation, we identified a series of differentially expressed metabolic genes. Metabolic genes are associated with tumor-related immune cells and clinical parameters, which might be therapy targets in future clinical application.

Comprehensive Analysis of Metabolic Genes in Breast Cancer Based on Multi-Omics Data