Systematic pan-cancer analysis identifies 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) as a biomarker of tumor invasion and metastasis, immunity, and prognosis

Abstract

Abstract 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a potent regulator of glycolysis in tumor cells, and high PFKFB3 expression is significantly associated with the invasion and metastasis of several tumors. However, there are no comprehensive reports on whether PFKFB3 promotes tumor invasion and its mechanism in different cancer types. In addition, there are no systematic reports on the effect of PFKFB3 on the stemness and immune infiltration ability of different tumors and on the survival rate of patients. Herein, we conducted a pan-cancer analysis of PFKFB3 with the aim of exploring the key cellular and molecular mechanisms regulating the pathogenesis and progression of human cancers, and propose potential strategies for the prevention and treatment of cancer by targeting PFKFB3. Using bioinformatics analysis and integrative exploration from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) databases, the differential expression of PFKFB3 or phosphorylated PFKFB3 and its correlation with tumor staging and stemness, survival prognosis, and immune invasion were extensively analyzed. The analysis showed differential expression of PFKFB3 in normal tissues and in various cancers. Increased PFKFB3 expression is positively correlated with the invasive ability and immune infiltration of 31 cancers and significantly affects the staging, stemness, prognosis, and survival rate of several cancers. Alterations in phosphorylated PFKFB3 and RNA modifications are also involved in the development and progression of various cancers. PFKFB3 is involved in multiple protein interactions and has complex molecular functions, such as ATP/ADP metabolic and glycolytic processes. Furthermore, PFKFB3 has a high mutation frequency, especially amplification, in multiple tumors. These findings highlight the significance of PFKFB3 in cancer progression, which might serve as a surrogate pan-cancer biomarker to predict the progression and outcome of cancers, as well as the invasion and immune infiltration of different cancers. Ethical compliance: This study did not involve any patient or animal samples and was approved by the academic committee of Tongji University.