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The Expression And Correlation Analysis Of HIF-1? And PD-L1 In Human Glioma

Posted on:2020-05-14Degree:MasterType:Thesis
Country:ChinaCandidate:D JiaFull Text:PDF
GTID:2404330590956085Subject:Surgery
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Background and Objective:Glioma is a tumor that originated in glial cells,is the most common primary brain tumors to date,surgery,radiotherapy and chemotherapy are three ways the treatment of glioma,despite the continuous improvement of glioma treatment.However,due to its special location,rapid tumor growth and strong invasiveness,the clinical treatment effect is not optimistic.With the development of tumor immunotherapy,immunotherapy of glioma has also attracted much attention..Programmed death 1,PD-1 is expressed in immune cells such as activated T lymphocytes and B lymphocytes.Programmed death ligand 1 is a ligand for PD-1,and PD-L1 expression can be detected in various human tumor tissues such as melanoma,breast cancer,and lung cancer.At present,Pembrolizumab,Nivolumab,Durvalumab,etc.for PD-1/PD-L1 have entered the clinical research stage,and have achieved gratifying results.Therefore,it is of great value to study the mechanism of PD-1/PD-L1 involved in glioma immune escape and the detection of related molecular markers for the diagnosis and prognosis of glioma.Hypoxia is an important feature of the microenvironment of solid tumors.The transcriptional regulation of hypoxia is mainly mediated by hypoxia-inducible factors(HIFs),and the expression of hypoxia-inducible factors-1?(HIF-1?)is the most abundant.It is ubiquitous and plays a key role as a regulatory subunit of oxygen homeostasis in many cell types.Studies have shown that the expression of PD-L1 is regulated by the hypoxic microenvironment.This experiment intends to analyze the relationship between PD-L1 and HIF-1?expression and clinical pathological features in clinical glioma tissue specimens by immunohistochemical method,further analyze the correlation between the two expressions and use the cancer genome mapping program(the cancer)The genome atlas,TCGA)database validation results,to explore the correlation ofHIF-1?on PD-L1 expression in glioma.Methods:Collected between 2010 and 2017,after the Shanxi Provincial People's Hospital neurosurgery underwent surgery,pathology results confirmed 43 cases of paraffin-embedded specimens of glioma patients.The age and sex of the patients in43 glioma specimens were counted.According to the WHO glioma grading,43 tissues were divided into low-level group and high-level group,and their tumor types were counted.The expression levels of PD-L1 and HIF-1?in glioma tissues were detected by immunohistochemistry.The data were analyzed by?~2 test and the correlation between HIF-1?and PD-L1 expression in gliomas.Using Spearman correlation analysis,the statistical results were compared with the TCGA database.Results:1.There were 19 cases in the low-level group and 24 cases in the high-level group,including 23 males and 20 females;the quartile method in the age reference,15persons less than 50 years old,28 or more than 50 years old;There were 25 cases of astrocytoma,12 cases of oligodendroglioma,and 6 cases of oligodendroglioma.2.The positive expression of HIF-1?in glioma tissues is brown and fine particles,and the staining is located in the nucleus.PD-L1 positive expression was brownish yellow particles,and the staining was localized to the cell membrane and/or cytoplasm.The positive expression rates of HIF-1?and PD-L1 in 43 glioma specimens were 58.13%(25/43)and 69.77%(30/43).HIF-1?expression was not associated with gender,age,tumor type,etc.(P>0.05),and was associated with pathological grade(P<0.05)?PD-L1 expression was not associated with gender,age,tumor type,etc.(P>0.05),and was associated with pathological grade(P<0.05)4.The positive rates of HIF-1?in different grades of glioma in 43 cases of glioma were 36.84%(7/19)in the low-level group and 75.00%(18/24)in the high-level group;PD-L1 was in different levels.The positive rates of glioma were 52.63%(10/19)in the low-level group and 83.33%(20/24)in the high-level group,respectively.The difference was statistically significant(P<0.05).5.Further analysis of HIF-1?and PD-L1 mRNA expression levels in 206 glioma patients in the TCGA database was found to be consistent with histochemical results(r=0.3215 P<0.05).Conclusion The study found that in clinical tissue samples glioma HIF-1?and PD-L1expression was positively correlated with the increase of the level of glioma,but also significantly increased the expression of both.Further positive correlations between HIF-1?and PD-L1 mRNA expression in gliomas were verified in the TCGA database.It is suggested that HIF-1?is involved in the regulation of PD-L1 expression in anoxic microenvironment.
Keywords/Search Tags:Glioma, Tumor microenvironment, Programmed death ligand
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