Expression Of Notch4, DLL4 And KAI1 In Non-small Cell Lung Cancer And There Relationship With Vasculogenic Mimicry

Purpose:Vasculogenic mimicry(VM)is a new blood supply style in tumors and has long been treated as a useful factor in malignant tumor metastasis and prognosis.Notch4(a marker of Notch signaling pathway receptors),DLL4(a marker of Notch signaling pathway ligands)and KAI1/CD82(a suppressor gene of tumor metastasis)are all effective predictive factors for tumor metastasis.In this study,we analyzed correlations among VM,Notch4,DLL4,and KAI1/CD82 in non-small cell lung cancer(NSCLC),and their respective associations with patients' clinicopathological parameters and survival rate in NSCLC.Methods:189 well-preserved NSCLC tissues and corresponding non-tumor lung tissues were detected by immunohistochemical staining.We observed and statistically analyzed VM structure and the positive expression rates of Notch4,DLL4 and KAI1/CD82.In addition,clinical data were collected and followed up.Data was analyzed using statistical software.Results:The positive rates of VM,Notch4 and DLL4 in NSCLC tissues were significantly higher than those in non-tumor lung tissues,while the positive expression levels of KAI1/CD82 in NSCLC were significantly lower than those in control non-tumor lung tissues.The positive rates of VM,Notch4,and DLL4 were positively correlated with tumor size,lymph node metastasis(LNM),distant metastasis(DM),and tumor TNM staging,and as opposed to postoperative total survival(OS).In addition,the positive rate of DLL4 was positively correlated with tumor grade.The positive expression level of KAI1/CD82 in tumor tissues was negatively correlated with tumor size,lymph node metastasis,distant metastasis and TNM stage.The total survival time of KAI1/CD82+ group was significantly higher than that of KAI1/CD82-group.In multivariate analysis,the presence of VM,high expression levels of Notch4 and DLL4,tumor size,LNM,DM,TNM stage,and low expression level of KAI1/CD82 may be independent prognostic factors for overall survival time(OST)in patients with NSCLC.In addition,the high expression of Notch4 and DLL4 was positively correlated with VM,and KAI1/CD82 expression was negatively correlated with VM.Conclusions:(1)VM structure and abnormal expression of Notch4,DLL4,and KAI1/CD82 in NSCLC is associated with the malignant biological behavior of NSCLC.(2)The high expression of Notch4 and DLL4 and the low expression of KAI1/CD82,which is beneficial to the formation of VM structure.(3)VM structure and combined detection of Notch4,DLL4,and KAI1/CD82 can be useful biomarkers for the prognosis of patients with NSCLC.