| Objective:Human glioma is the most common malignant tumor of the central nervous system,accounting for more than 80% of the primary malignant tumors of the central nervous system,with the characteristics of strong invasion and high recurrence rate.Despite the extensive use of surgical treatment to the maximum extent,and chemotherapy and radiotherapy were carried out after operation.However,the tumor is still prone to recurrence and the patient has a poor prognosis.Currently,with the development of molecular biology and molecular pathological diagnosis,it is particularly important to diagnose and treat gliomas from a molecular perspective.SQSTM1/P62 is a multifunctional scaffold protein that is involved in many different cellular processes,including selective autophagy,antioxidant response,endosome transport,inflammation,and apoptosis.P53 acts as a transcription factor and regulates biological processes involved in cell growth,senescence,and apoptosis.In this study,the expression of SQSTM1/P62 and P53 in human glioma was detected by immunohistochemical staining,so as to explore the expression of SQSTM1/P62 and P53 in human gliomas with different pathological grades,analyze their correlation and clinical significance and provide valuable molecular markers for the diagnosis and treatment of glioma.The PDX model of human glioma was established to study the expression characteristics of SQSTM1/P62 and P53 in PDX tissue,providing a valuable technical platform for further study of their roles in tumor development.Methods:1.50 samples with human glioma surgically removed from Neurosurgery Department of Affiliated Hospital of Hebei University from May 2016 to May 2019 were collected.According to the WHO(2016)Classification Standard for Glioma(4th edition),they were divided into two groups: the low-grade group(WHO gradeⅠ-Ⅱ)for 22 cases,the high-grade group(WHO grade Ⅲ-Ⅳ)for 28 cases.Immunohistochemical SP method was used to detect the expression of SQSTM1/P62 and P53 in glioma,and statistical methods was used to analyze the relationship between them and pathological level,as well as their relationship in glioma tissue.2.Intracranial orthotopic transplantation was used to transplant patient-derived tumor cells into the brain of nude mice,and the glioblastoma PDX model was successfully established by orthotopic transplantation.Immunohistochemical SP method was used to detect the expression of SQSTM1/P62 and P53 protein in tumor tissue of PDX model.Results:1.The positive rates of SQSTM1/P62 in 50 human glioma tissues were 22.73%(5 / 22)and 82.14%(23 / 28)in the low-grade human glioma group and the high-grade human glioma group,respectively.The expression of SQSTM1/P62 in the high-grade human glioma group was significantly higher than that in the low-grade human glioma group,with a significant difference(χ2=17.651,P﹤0.05).2.The positive rates of P53 in 50 human glioma tissues were 13.64%(3 / 22)and 42.86%(12 / 28)in the low-grade human glioma group and the high-grade human glioma group,respectively.The expression of P53 in the high-grade human glioma group was significantly higher than that in the low-grade human glioma group,with a significant difference(χ2=5.009,P﹤0.05).3.The expression of SQSTM1/P62 was positively correlated with the expression of P53(rs = 0.317,P﹤0.05),namely the expression of SQSTM1/P62 and P53 were increased in glioma tissue.4.The PDX model was established successfully.The positive expression rate of SQSTM1/P62 in PDX tumor tissue was(35.63 ± 3.45)%,and that in glioblastoma tissue with the same origin was(33.07 ± 6.40)%(P > 0.05)The positive expression rate of p53 in PDX tumor tissue was(7.84 ± 2.22)%,and that in glioblastoma tissue with the same origin was(6.79 ± 1.77)%(P > 0.05).Conclusion:1.The expression of SQSTM1/P62 and P53 in glioma is related to the grade of glioma.Both of them can be used as ideal molecular markers to predict the malignancy of glioma.2.The expression of SQSTM1/P62 is positively correlated with P53 in glioma.They play a synergistic role in promoting the occurrence and development of glioma,of which potential mechanism may be related to the inhibition of autophagy in glioma.3.There is no significant difference between the autophagy and apoptosis ability of PDX model tumor tissue and that in glioblastoma tissue with the same origin.PDX model retains the biological characteristics of the primary tumor and provides an ideal technical platform for the individualized studies of glioma. |
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