6-phosphofructo-2-kinase as therapeutic targets in cancer based on an integrated pan-cancer study6-phosphofructo-2-kinase as therapeutic targets in cancer based on an integrated pan-cancer study

Abstract Background: Warburg effect confirm that tumor cells prefer to use glycolysis to perform metabolism glucose metabolism. PFKFB enzymes involve the activity of 6-phosphofructo-1-kinase in the metabolism of glycolysis. But their roles in immunity and the regulation of tumor microenvironment has not been fully understood. Methods: We performed a comprehensive analysis of PFKFB in with immune subtypes, tumour microenvironment, and drug sensitivity from data of pan-cancer. Data of 33 cancer subtypes including RNA-Seq, clinical phenotype, stemness scores of mRNA (RNAss) and DNA-methylation (DNAss), and immune subtypes was downloaded from TCGA. NCI-60 data and RNA-seq data were acquired from the CellMiner. Perl language and R language with packages were used to deal with data. Results: Expression of PFKFB family emerges different heterogeneity in different cancer. PFKFB1, PFKFB3 and PFKFB4 predicted poor prognosis of patients with multiple cancers. All members are associated with immune response. PFKFB3 and PFKFB4 involved tumor microenvironment of pan-cancer. Importantly, our study found that PFKFB genes, especially PFKFB2 and PFKFB4 may contribute to drug resistance in cancer cells. Conclusions: PFKFB family member possess special characters in each cancer based on gene expression and their correlation with immune infiltrates, tumor microenvironment. PFKFB2 and PFKFB4 may act as therapeutic targets in cancer.