| Research background and purpose:Head and neck tumors are one of the common malignant tumors worldwide,involving multiple organs of the head and neck with complex and diverse pathological types,among which squamous cell carcinoma is the most common,accounting for more than 90%.According to 2020 data,head and neck squamous cell carcinoma(HNSCC)has the eighth highest incidence and the twelfth highest mortality rate of malignant tumors worldwide,with an incidence of about 840,000,which is expected to rise to about 1 million by 2030.In 2020,China will have 142,000 new head and neck cancer patients,ranking ninth in incidence rate,second only to thyroid cancer,which ranks eighth and is on a steady rise,with nearly 75,000 deaths.For head and neck squamous carcinoma,despite the use of a multidisciplinary combination of surgery,radiotherapy,chemotherapy,targeted and immunotherapy,approximately 20% of patients with early stage disease and 50% of patients with locally advanced disease still develop recurrence or metastasis during the course of the disease.The prognosis of recurrent or metastatic head and neck squamous carcinoma is poor,with a median overall survival time(OS)of about 1 year.Although a lot of basic and clinical research has been done,the specific mechanism of metastasis of head and neck squamous carcinoma is not clear,so if the specific metastasis of head and neck squamous carcinoma or its promoting or inhibiting factors can be clarified,it can provide new ideas and new means for the diagnosis and treatment of more patients,which is of great significance to improve the prognosis of patients.Epithelial membrane protein 2(EMP2)is a cell surface protein consisting of approximately 160 amino acids,consisting of two extracellular structural domains,a small cytoplasmic tail,and three putative N-chain glycosylation sites,encoded by the growth arrest-specific 3(GAS3)/peripheral myelin protein 22 k Da(PMP22)gene family,with the human gene localized to chromosome 16(16p13.13-13.2),which is 52.3 Kb long,contains 4 exons,5.2 kb long c DNA,and an EMP2 molecular weight of approximately 19 KD.According to the human protein atlas,EMP2 expression varies between organs,with the highest m RNA levels in type I alveolar cells,and EMP2 expression is not always uniformly expressed in individual organs;for example,the eye is expressed in the cornea,sclera,and iris,but not in the lens or retina.altered EMP2 expression has been demonstrated in several pathological diseases,including tumors,nephropathy syndrome,placental insufficiency,and pathological neovascularization of the retina.Although EMP2 expression has been studied in several diseases,the mechanism of action and the extent of its role in pathogenesis remain unclear.The study of the functional role of EMP2 in the occurrence,development,invasion,metastasis and radiosensitivity of HNSCC and the related mechanisms is still in a blank stage.Further study of the related functions and mechanisms of EMP2 gene may provide new theoretical basis and new strategies for the molecular diagnosis and targeted therapy of HNSCC,which has great practical and clinical significance.In this study,we investigated the expression of EMP2 in HNSCC,transfected human head and neck squamous cell carcinoma cells with EMP2 overexpression lentiviral vector,and explored the effects of EMP2 overexpression on proliferation,apoptosis,invasion,migration-related biological properties and radiosensitivity of head and neck squamous cell carcinoma cells,aiming to provide a theoretical basis for the diagnosis and treatment of EMP2 in head and neck squamous cell carcinoma.Materials and Methods:Expression of EMP2 in head and neck squamous cell carcinoma tissues andcells.Bioinformatics analysis,mining of public databases and analysis of EMP2 expression in HNSCC patients yielded that EMP2 is lowly expressed in head an d neck squamous cell carcinoma and highly expressed in surrounding normal tiss ues.Effects of EMP2 on some biological functions of head and neck squamous c arcinoma cells.EMP2 perk up can inhibit the growth of head and neck squamou s cell carcinoma cells,promote apoptosis of tumor cells,and inhibit the invasiveability of laryngeal tumor cells,suggesting that it functions as a tumor suppress or gene Effect of EMP2 combined with radiation therapy on the sensitivity of he ad and neck squamous carcinoma cells to radiotherapy.High expression of EMP2increased the radiosensitivity of head and neck squamous carcinoma cells compa red to low expression of EMP2.Results:1.Expression of EMP2 in head and neck squamous cell carcinoma tissues and its relationship with patient survival time.By mining and analyzing the expression of EMP2 in HNSCC patients in TCGA and Starbase databases,we learned that EMP2 expression in head and neck squamous cell carcinoma tissues is lower than in adjacent normal tissues.In the GEPIA database,it was found that EMP2 expression was correlated with DFS,and EMP2 expression had longer DFS.2.Effects of overexpression of EMP2 on some biological functions of head and neck squamous cell carcinoma cells.The CCK8 test showed that overexpression of EMP2 could inhibit the proliferation of human head and neck squamous cell carcinoma cells.The cell scratch and Transwell tests confirmed that the migration and invasion ability of head and neck squamous cell carcinoma cells was significantly inhibited after overexpression of EMP2 compared with the control group.In summary,it is suggested that EMP2 exerts the function of tumor suppressor gene.3.Effects of overexpression of EMP2 in combination with radiotherapy on some biological functions of head and neck squamous cell carcinoma cells.The clonal formation test of plate showed that overexpression of EMP2 could inhibit the clonal formation of head and neck squamous cell carcinoma cells,and emp2 was found to have a synergistic effect on radiotherapy in combination with radiotherapy.The detection of apoptosis by flow cytometry showed that overexpression of EMP2 promoted apoptosis of human head and neck squamous cell carcinoma cells,and after combination with radiotherapy,it was found that the apoptosis rate increased significantly.In summary,EMP2 overexpression combined with radiotherapy can increase the radiosensitivity of head and neck squamous cell carcinoma.Conclusions:1.EMP2 was lowly expressed in head and neck squamous carcinoma tissues,and bioinformatics analysis showed that the protein expression status of EMP2 was negatively correlated with the clinical stage and prognosis of patients.2.In vitro experiments have shown that upregulation of EMP2 expression can inhibit tumor cell growth and proliferation,migration and invasion,and promote apoptosis,and low expression of EMP2 in head and neck squamous carcinoma patients can be used as one of the indicators of poor prognosis.3.EMP2 overexpression combined with radiotherapy can increase the radiosensitivity of head and neck squamous carcinoma cells. |
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