The influence of PFK-II overexpression on neuroblastoma patients' survival may be dependent on the particular isoenzyme expressed, PFKFB3 or PFKFB4

Abstract

Background/Aim: During cancer progression metabolic reprogramming is observed in parallel to the alternation in transcriptional profiles of malignant cells. Recent studies suggest that metabolic isoenzymes of phosphofructokinase II (PFK-II) - PFKFB3 and PFKFB4, often induced in hypoxic environment, significantly contribute to enhancement of glucose metabolism and in consequence cancer progression. Materials and methods: Using the publicly available data deposited in the R2 data base we performed a Kaplan-Meyer analysis for cancer patients divided into groups with high and low expression levels of PFKFB3/4, determined based on the median. Results: Our data showed that high PFKFB3/4 expression significantly correlates with shorter overall survival in several cancers. Moreover, we found that neuroblastoma patients with poor overall survival and evidence free survival are characterized by high PFKFB3 and at the same time low PFKFB4 expression, whereas patients with high PFKFB4 expressions are characterized by significantly better overall survival/evidence free survival rates. Conclusion: Our analysis clearly indicates that expression of PFKFB3/4 isoenzymes may have a key prognostic value for several cancers. What's more, it seems that in neuroblastoma the prognostic value of PFK-II may be dependent on the relation between PFKFB3 and PFKFB4 isoenzyme expression, indicating that further studies analyzing the role of both cancer specific PFK-II isoenzymes are highly desired.