Expression Of LTA4H In Esophageal Squamous Cell Carcinoma And Its Clinical Significance

ObjectiveThe aim of this project was to investigate the expression and clinical significance of Leukotriene A4 Hydrolase(LTA4H)in Esophageal squamous cell carcinoma(ESCC),and to provide experimental basis for the discovery of novel esophageal cancer biomarkers and explore new individualized targeted therapy strategies.MethodsThe expression of LTA4 H in esophageal cancer and normal paracancerous epithelial tissues was determined by tissue microarray and immunohistochemistry.Survival analysis and immunohistochemical staining were combined to investigate the relationship between LTA4 H expression in esophageal cancer and patient survival as well as the pattern of its expression.Multivariate Cox regression was used to predict the risk of each clinicopathological parameter.The expression of LTA4 H at the m RNA level in esophageal cancer cells was detected with q PCR,and esophageal cancer cell lines with high and low expression of LTA4 H gene were screened.Redults1.Immunohistochemical results showed that LTA4 H was highly expressed in cancer cells of ESCC patients compared with normal paracancerous esophageal epithelium.2.Univariate Kaplan-Meier statistical analysis showed that strong expression of LTA4 H was significantly negatively correlated with survival of ESCC patients(P<0.05).3.Compared with patients’ clinicopathological data,it was shown that the expression of LTA4 H was significantly and positively correlated with lymph node metastasis(P=0.001)and p TNM(P<0.001)stages in ESCC patients;the positive expression rate of LTA4 H in stages III-IV was 16.5%(22/133),which was higher than that in stages I-II(7.9%)(13/164,P=0.029).Another result showed that the positive expression rate of LTA4 H in ESCC patients with lymph node metastasis was16.3%(24/147),which was higher than the positive expression rate of 7.3%(11/150,P=0.019)in cases without lymph node metastasis.4.The results of Cox multifactorial risk analysis showed that the positive expression of LTA4 H was an independent risk factor for the prognosis of ESCC patients(Risk=1.333,95%CI=1.023-1.737,P=0.033).Among them,tumor size(Risk=0.583,95%CI=0.406-0.838,P=0.014),lymph node metastasis(Risk=2.009,95%CI=1.537-2.624,P<0.001),TNM staging(Risk=1.941,95%CI=1.941,95%CI=1.941,P<0.001),and lymph node metastasis(Risk=2.009,95%CI=1.537-2.624,P<0.001),TNM stages(Risk=1.941,95%CI=1.491-2.527,P<0.001)and histology of tumor tissue differentiation(Risk=0.407,95%CI=0.245-0.677,P=0.001)were all independent risk factors,with special emphasis on age as an independent prognostic factor for ESCC patients as well(Risk=0.316,95% CI=1.014 to 1.709,P=0.039).And patient gender,tumor location,and depth of tumor infiltration were not independent risk factors in determining the prognosis of ESCC patients(P=0.756,0.987,0.683).5.q PCR analysis of the expression of LTA4 H gene in esophageal cancer cell lines KYSE150,TE1,Eca-30,Eca-70,Eca-180,Eca-450 showed that LTA4 H gene was highly expressed in esophageal cancer cell lines Eca-30 and Eca-450,while it was weakly expressed in esophageal cancer cell line TE1 and Eca-70.ConclusionsOur study found that LTA4 H was highly expressed and positively correlated with esophageal squamous cell carcinoma and negatively correlated with patient prognosis,suggesting that LTA4 H may play an important role in the development of esophageal carcinoma,and is a new potential biomarker for diagnosis and prognosis of esophageal cancer and a new potential target for targeted therapy.