Aberrant expression of 5-lipoxygenase-activating protein (5-LOXAP) has prognostic and survival significance in patients with breast cancer

Abstract

5-lipoxygenase (5-LOX)-activating protein, 5-LOXAP also known as LOX5AP or FLAP, is a protein that works closely with 5-LOX in regulating the metabolism of arachidonate. Some of the eicosanoid products of 5-LOX/5-LOXAP are known to play active roles in the function of cancer cells, including breast cancer cells. The current study investigated the expression of 5-LOXAP in clinical breast cancer and the prognostic impact of 5-LOXAP and 5-LOX in patients with breast cancer. A cohort of breast tumour tissues ( n = 1 2 2 ) with normal background tissues ( n = 3 2 ) were investigated. 5-LOXAP and 5-LOX transcripts were determined using RT-PCR and quantitative RT-PCR. Levels of the transcripts were analysed against clinical and pathological information. Breast tumour tissues had significantly higher levels of 5-LOX transcript compared with normal tissues ( P = 0.0 1 5 ). The transcript was seen at significantly higher levels in node positive tumours than that in node negative tumours ( P = 0.0 2 ). The prognostic significance was assessed using both a prognostic index and clinical outcome. Value of 5-LOXAP was first demonstrated when using the Nottingham Prognostic Index (NPI) as an indicator, in that patients with predicted poor prognosis had significantly higher levels of 5-LOXAP than patients with good prognosis ( P = 0.0 4 0 7 ). Furthermore, patients who died of breast cancer-related causes had significant higher levels of 5-LOXAP than those patients who remained disease free, following a median 10-year followup. A survival analysis has shown that high levels of 5-LOXAP were significantly correlated with overall survival (mean survival 109.6 month vs. 139.4 months, in tumour from patients with high and low levels of 5-LOXAP, P = 0.0 5 ). The same disadvantage of high levels of 5-LOXAP was also seen with disease-free survival (105.2 months vs. 135.6 months, P = 0.0 1 7 ). Analysis of 5-LOXAP together with 5-LOX transcript did not enhance the significance of the survival. However, when 5-LOXAP was considered together with 12-LOX, it improved the predictive power for both overall and disease-free survival (109.0 month vs. 143.1 months, P = 0.0 1 5 6 for overall survival and 98.3 months vs. 141.3 months for disease-free survival, P = 0.0 0 2 2 ). In conclusion, 5-LOXAP expression was aberrant in human breast cancer, particularly in aggressive tumours. Furthermore, 5-LOXAP had a significant prognostic value in patients with breast cancer. This identifies 5-LOXAP as a potential therapeutic target in breast cancer.