| Objective:To study the expression of genes and proteins related to NLRP3-mediated classical pyroptosis pathway in epithelial ovarian cancer;To explore the role and potential value of the classical pyroptosis pathway in the development of epithelial ovarian cancer and in the treatment.Methods:In the fiest part,select Ovarian tissue paraffin specimens that underwent first debulking surgery in our hospital from June 2013 to May 2021 and which postoperative pathology was confirmed to be epithelial ovarian cancer;Select Ovarian paraffin specimens that were underwent Oophorectomy surgery in our hospital that postoperative pathology was confirmed normal tissue.Study differences in expression of initiator nucleotide oligomerization receptor P3(NLRP3)by immunohistochemistry,which related to the classical cytokinesis pathway.Explore its relevance to tumor staging,metastasis,etc.The results were statistically analyzed with SPSS26.0.In the second part,exploring and verifing the differences of pyroptosis related genes between ovarian cancer and normal ovarian tissues that based on GEO database,TCGA database and Gene Cards database.Then,exploring differential gene survival analysis in Kaplan-Meier Plotter database;Do ss GSEA enrichment analysis based on TCGA database;Finally,preliminary immune invasion analysis is performed in TIMER database and verifying them in TCGA database.Some of the data analysis was performed using R software(Version3.6.3).Results:1.The expression of NLRP3 was significantly different in normal ovarian tissue and epithelial ovarian cancer,but there is no significant correlation between patient age,tumor stage,and omental metastasis;2.In epithelial ovarian cancer,15 pyroptosis-related encoding genes showed differential expression compared with normal ovarian tissues,including encodes genes of Gasdermin D:GSDMD,the key effector protein in the classical pyroptosis pathway,and IL18 which encoding the important effector molecule:IL-18;3.GSDMD and IL18 in epithelial ovarian cancer have positive significant correlation with the overall survival of patients;4.Enrichment analysis showed that IL18 was able to enhance the activation of T cell receptor complexes as well as naturally killer cell-mediated immune responses;5.Through the analysis of 24 kinds of immune cells in the tumor immune microenvironment(TEM),GSDMD affects the expression of 22 kinds of immune cells,including T cells,B cells,helper T cells(Th),natural killer cells(NK);IL18 can promote the expression of 19 kinds of immune cell functions such as T cells and macrophages Conclusions:In epithelial ovarian cancer,pyroptosis is a protective factor for patient survival,and has an irreplaceable effect on the construction of the tumor immune microenvironment,may become a new target for immunotherapy and tumor resistance reversal. |
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