High expression of metabolic enzyme PFKFB4 is associated with poor prognosis of operable breast cancer

Abstract

Background: Enhanced glycolysis in tumors, known as the Warburg effect, provides the metabolic basis of enhanced cancer cell proliferation and metastasis. The Warburg pathway enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a newly identified key kinase that regulates transcriptional reprogramming and cell proliferation. Here we show the prognostic value of PFKFB4 expression in patients with operable breast cancer. Methods: PFKFB4 expression was evaluated by immunohistochemistry in surgical specimens retrospectively collected from 200 patients with histologically proven invasive ductal breast cancer. Kaplan-Meier survival analysis and Cox regression analysis were performed to assess the prognostic significance of PFKFB4 expression. Results: Kaplan-Meier survival analysis revealed that breast cancer patients with high PFKFB4 expression demonstrated unfavorable disease-free survival (p = 0.008) and overall survival (p = 0.002). PFKFB4 had an hazard ratio (HR) of 7.38 (95% CI 1.69-32.3; p = 0.008) in univariate Cox analysis and retained prognostic power (HR 7.44, 95% CI 1.67-33.2; p = 0.009) when adjusted by tumor size, lymph node status, grade, estrogen receptor status, human epidermal growth factor receptor 2 status and subtype, which indicated PFKFB4 was an independent prognostic factor in breast cancer. Conclusions: Together, our findings establish the prognostic value of metabolic enzyme PFKFB4 in patients with operable breast cancer.