Integrated analysis of gene correlation reveals disordered relationship between metabolism and immunity in tumor microenvironment

Background Metabolism reprogramming and immune evasion are the most fundamental hallmarks for cancer survival. The complex interactions between metabolism and immune systems in tumors and their microenvironment is complicated. Researching on the correlation changes between metabolic and immune related-genes in normal and tumor tissues would help to reveal these complex interactions. Methods In this study, the mRNA profiles across 11 cancer types was obtained from The Cancer Genome Atlas (TCGA). Then, the spearman’s correlation coefficient was calculated between metabolic and immune related-genes for each sample group. Results Our results showed that the number of correlated gene pairs was reduced significantly in tumor tissues compared with those of normal tissue, especially in KIRC, KIRP and STAD. Functional enrichment analysis for the universal (the pairs appeared in more than 2 cancer types) and specific (the pairs only in one specific cancer type) gene pairs across cancer types revealed top pathways which appeared in tumor and normal samples, such as phosphatidylinositol signaling system and inositol phosphate metabolism. Thereinto, the pairs in normal tissues missing in tumors may indicate they are important factors affecting immune system, such as, DGKs and PIP4ks. The correlation analysis between immune checkpoint and metabolism genes also showed a reduced correlation in tumor and had the tissue specificity, such as, FUT8 was strongly correlated with PDCD1 in the HC of STAD and they had a weaker correlation in other normal tissues and tumor types. Conclusions Our study provides a novel strategy for investigating interaction of tumor immune and metabolism in microenvironment and offers some key points for exploring new targets including metabolic targets and immunomodulator of immune checkpoints. * HNSC : Head and Neck Squamous Cell Carcinoma KIRC : Kidney Renal Clear Cell Carcinoma KIRP : Kidney Renal Papillary Cell Carcinoma LIHC : Liver Hepatocellular Carcinoma LUAD : Lung Adenocarcinoma LUSC : Lung Squamous Cell Carcinoma STAD : Stomach Adenocarcinoma THCA : Thyroid Carcinoma. BRCA : Breast Invasive Carcinoma CRC : Colorectal Carcinoma HC : Healthy Control TCGA : The Cancer Genome Atlas TME : Tumor Microenvironment DGKs : Diacylglycerol Kinases PIP4ks : Phosphatidylinositol-5-Phosphate 4-Kinases FUT8 : Fucosyltransferase 8 TNFRSF4 : TNF Receptor Superfamily Member 4 CTLA4 : Cytotoxic T-Lymphocyte Associated Protein 4 PDCD1 : Programmed Cell Death 1 CD274 : Programmed Cell Death Ligand 1 DGKA : Diacylglycerol Kinase Alpha PIP4K2C : Phosphatidylinositol-5-Phosphate 4-Kinase Type 2 Gamma HIF1A : Hypoxia Inducible Factor 1 Subunit Alpha IL4I1 : Interleukin 4 Induced 1