Nectin-4 Expression In Head And Neck Squamous Cell Carcinoma And The Effects Of Nectin-4 On The Poliferation And Migration Of Human Head And Neck Squamous Cell Carcinoma Cells

BackgroundHead and neck squamous cell carcinomas(HNSCC)are the sixth most common malignant tumors worldwide,in which more than 650,000 new cases diagnosed each year,often in advanced stages.In recent years,there have been advances in diagnosis and treatment,but the overall survival rate for patients with advanced HNSCC is still only 65%,with an overall 5-year survival rate of less than 50%.The important factors include the high recurrence rate and metastasis possibility of HNSCC after traditional therapy,which affect the survival rate of HNSCC.And the combined therapy with radiotherapy and chemotherapy has various complications,which affects the quality of life.Therefore,it is important to elucidate the molecular mechanism of HNSCC and explore more appropriate tumor molecular markers,which in order to improve the individualized therapy of HNSCC.Nectin-4 is a kind of cell adhesion molecule,which is commonly seen in malignant carcinoma with poor prognosis.A number of experiments have shown that the inhibition of nectin-4 synthesis can inhibit cell growth and the formation of lamellar pseudopodia and reduce the ability of cell migration.However,it is not clear whether nectin-4 is involved in the invasion and metastasis of HNSCC and whether it mediates epithelial-mesenchymal transformation.Objective1.To investigate the expression of nectin-4 in HNSCC,and analyze the clinical and prognostic significance of nectin-4 expression in HNSCC patients.2.To explore the effect of nectin-4 expression on the malignant biological characteristics of HNSCC cells and its underlying mechanisms.Methods1.Using bioinformatics database and IHC to examine the expression profile and clinical data of HNSCC patients,to analyze the relationship between nectin-4 differential expression and clinicopathological parameters,and to explore the prognostic value of nectin-4 expression in HNSCC patients.2.To quantificationally detect the expression of nectin-4 in HNSCC lines(UM-SCC-47、Fadu、Hep-2、HNE1)and human normal bronchial epithelial cells(HBE)by real-time PCR and Western blotting.Suppression the expression of nectin-4 in HNSCC cells using siRNA.And then,to investigate the effects of nectin-4 interference and detect cell proliferation,migration and invasion in vitro by CCK-8,cloning formation experiments.3.To detect the expression changes of AKT after interference nectin-4.Results1.Database mining results and IHC results showed that nectin-4 expression is elevated in HNSCC tissues.Patients with high nectin-4 expression showed significantly shortened recurrence-free survival time,overall survival time and metastatic relapse free survival time.2.The expression levels of nectin-4 mRNA and protein in HNSCC cancer cell line UM-SCC-47,Fadu,Hep-2 and HNE1 were significantly higher than those in normal bronchial epithelial cells HBE.3.Interfering nectin-4 expression significantly suppresses proliferation,migration and invasion abilities of HNSCC cells.4.Nectin-4 was positively correlated with AKT,which possibly mean nectin-4 activates PI3K/AKT signaling pathways in HNSCC cells.ConclusionThe elevated expression of nectin-4 was found in HNSCC,which was related to poor prognosis of patients.Nectin-4 could promote proliferation and migration of HNSCC cells,and may be involved in activation of PI3K/AKT signaling pathways.Therefore,nectin-4 may be served as a potential prognostic biomarker and therapeutic target of patients with HNSCC cancer.