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 () with normal background tissues () 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 (). The transcript was seen at significantly higher levels in node positive tumours than that in node negative tumours (). 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 (). 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, ). The same disadvantage of high levels of 5-LOXAP was also seen with disease-free survival (105.2 months vs. 135.6 months, ). 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, for overall survival and 98.3 months vs. 141.3 months for disease-free survival, ). 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. [Copyright &y& Elsevier]