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

Abstract

BackgroundEnhanced 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.MethodsPFKFB4 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.ResultsKaplan–Meier survival analysis revealed that breast cancer patients with high PFKFB4 expression demonstrated unfavorable disease-free survival (p\u2009=\u20090.008) and overall survival (p\u2009=\u20090.002). PFKFB4 had an hazard ratio (HR) of 7.38 (95% CI 1.69–32.3; p\u2009=\u20090.008) in univariate Cox analysis and retained prognostic power (HR 7.44, 95% CI 1.67–33.2; p\u2009=\u20090.009) 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.ConclusionsTogether, our findings establish the prognostic value of metabolic enzyme PFKFB4 in patients with operable breast cancer.