Expression Of 5-lipoxygenase Activating Protein(5-LOXAP) In Esophageal Squamous Cell Carcinoma And Its Clinical Significance

Objective5-lipoxygenase activator protein(FLAP)can activate 5-lipoxygenase and provide substrate for 5-oxygenase.Arachidonic acid presented to 5-LO and transformed into 5-hydroperoxide eicosapentaenoic acid(5-HPETE)。Leukotriene A4(LTA4)produces LTB4,LTC4,LTD4 and LTE4 under the action of hydrolase and synthetase Leukotriene can cause the increase of mucus secretion contraction of blood vessels and smooth muscles,increase of vascular permeability,aggregation of eosinophils and proliferation of fibroblasts.A large number of studies have shown that FLAP and 5-LO gene polymorphisms are closely related to atherosclerosis,asthma,rhinitis,and many other diseases.The expression of 5-LO and FLAP was detected in cancer cells,lung cancer cells,colon cancer cells and prostate cancer cells.Flap can induce apoptosis of breast cancer and pancreatic cancer cells.However,there are few reports on the relationship between flap and esophageal squamous cell carcinoma.We provide new clues for the auxiliary diagnosis,prognosis and treatment of esophageal squamous cell carcinoma by studying the expression of 5-LO metabolic pathway flap enzyme protein and esophageal squamous cell carcinoma(ESCC).Objective to investigate the effect of MK886,a flap inhibitor,on the proliferation of human esophageal cancer cell line kyse-150.MethodsGoat anti-human polyclonal 5-LO antibody(Santa Cruz Biotechnology,Germany)and Super Pic Ture Polymer Detection kit and the Liquid Substrate kit(Invitrogen,Carlsbad,USA)were carried out according to the peration manual,and finally observed and photographed under the optical microscope.The experimentaldata were SPSS(version 13.0)mean SD)excel Pearson Chisquare o KAP 1 an-Meier,univariate survival analysis and Cox multivariate survival analysis.all P values were tested by bilateraltest,P value less than 0.05 was statistically significant resultln normal esophageal epithelium,FLAP was mainly located in the cytoplasm close to the cell membrane.Esophageal cancer cell line kyse-150 was cultured,and different concentrations of FLAP inhibitor MK886 were used to intervene in vitro.Cell proliferation was measured by xcelligence RTCA system.Results1.Compared with the normal esophageal epithelium,the expression of flap in ESCC changed from local to whole cytoplasm,and the expression level of flap protein was significantly increased.In 297 cases of ESCC,74 cases(24.9%)showed negative or weak positive expression of flap(0-2 points),223 cases(75.1%)showed strong positive expression of flap(3-12 points),while in normal esophageal epithelial tissues,only 20%samples expressed flap;2.Kaplan Meier statistical analysis showed that the expression of FLAP was negatively correlated with the survival time of patients with esophageal squamous cell carcinoma(P<0.05);3.Further analysis showed that the expression of flap protein was positively correlated with regional lymph node metastasis(P=0.001)and clinical pTNM stage(P<0.001);4.Univariate and multivariate analysis showed that the expression of flap was an independent prognostic factor in esophageal squamous cell carcinoma(P=0.026),which could be used as an important reference factor in predicting the prognosis.It is suggested that the increased expression of flap may play an important role in the occurrence and development of esophageal squamous cell carcinoma.Detection of the expression of flap can warn the prognosis of patients with esophageal squamous cell carcinoma;5.The high expression rate of flap in ESCC was similar in Chaoshan area of Guangdong Province and Chifeng region of Inner Mongolia,with 69.3%in Chifeng area,slightly lower than 75.1%in Shantou area of Guangdong Province.6.A certain concentration of FLAP inhibitor MK886 could significantly inhibit the proliferation of esophageal cancer cell kyse-150(P<0.05).ConclusionsFLAP plays an important role in the occurrence and development of esophageal squamous cell carcinoma(ESCC).The expression of FLAP in esophageal squamous cell carcinoma can better judge the prognosis of patients with esophageal squamous cell carcinoma,and it is a new biomarker to warn the prognosis of esophageal squamous cell carcinoma.FLAP inhibitor(MK886)can inhibit the proliferation of human esophageal cancer cells,which provides a theoretical reference for clinical medication.