Clinical Application Of MMR And P53 Detection In Endometrial Cancer And The Research Of Differentially Expressed Genes

Purposes:This study retrospectively analyzed the clinical data of endometrial cancer(EC)diagnosed pathologically by the Yuebei People Hospital affiliated to Shantou University,and through MMR and p53 immunohistochemistry to classify endometrial cancer,aiming to explore and simplify the clinical practice feasibility of the ProMisE molecular classification and the value of judgment for survival and prognosis.Methods:A total of 219 EC patients diagnosed and treated in the Department of Gynecology,Yuebei People Hospital from January 2018 to December 2020 were collected,and the paraffin specimens obtained were subjected to mismatch repair(MMR)and Tp53 immunohistochemistry(IHC)check.According to the results of MMR and p53 IHC,they were divided into MMR-defective(MMR-d),p53 abnormal(p53abn)and p53 wild type(p53wt).Collect and sort out clinical data,pathological data and follow-up information.Apply Med Calc18.2.1 statistical analysis software to analyze the correlation between the simplified ProMisE molecular subtypes and clinical and pathological features,and summarize the relevant factors that affect the prognosis.Results:1.According to the classification sequence of ProMisE,219 endometrial cancer patients were simplified into three types: MMR-d,p53 wt and p53 abn through MMR and p53 immunohistochemical detection.There are 53 cases of MMR-d patients,accounting for 24.20%;98 cases of p53 wt,accounting for 44.75%;68 cases of p53 abn,accounting for 31.05%.2.The incidence of p53 abn combined with diabetes was significantly higher than that of p53 wt and MMR-d,and the difference was statistically significant(P=0.035).p53 abn retroperitoneal lymph node metastasis was significantly higher than that of MMR-d and p53 wt,and the difference was statistically significant(P=0.002);the FIGO staging of p53 abn was significantly higher than that of MMR-d and p53 wt,and the difference was statistically significant(P=0.038).The comparison of the three subtypes of simplified ProMisE in clinical characteristics such as age,BMI,number of deliveries,and pathological characteristics such as the depth of muscle invasion,cervical interstitial involvement,adnexal metastasis,and vascular space involvement were not statistically significant..3.Univariate analysis uses Kaplan-Meier and Logrank to analyze the correlation between subtypes and survival.The results show molecular classification,traditional pathological classification,grade,FIGO staging,depth of myometrial invasion,LVSI,ER,PR,diabetes,retroperitoneal lymph node metastasis are all related to the prognosis.COX multivariate analysis showed that grade,vascular infiltration,and depth of myometrial invasion were independent risk factors affecting the prognosis of EC.Conclusions:The simplified ProMisE classification has a certain guiding effect on the prognosis of EC.p53 abn is related to high FIGO staging and high retroperitoneal lymph node metastasis,and has the worst survival prognosis among the simplified ProMisE subtypes;COX multivariate analysis shows the degree of tissue differentiation,vascular infiltration and tdepth of myometrial invasion are independent risk factors that affect the survival and prognosis of endometrial cancer.Purposes:Our study intends to use bioinformatics methods combined with immunohistochemistry techniques to find the core differential genes in the process of endometrial cancer,and to provide a basis for further improving the molecular classification and risk stratification of endometrial cancer.Methods:RNA-seq technology was used to detect differentially expressed genes(DEGs)in endometrioid adenocarcinoma and normal endometrial tissue samples.GO(Gene Ontology)and KEGG were used for enrichment analysis,and the String network was used to perform PPI on differential genes.Network construction 20 core genes were screened on the basis of PPI network,and preliminary verification was carried out by immunohistochemistry.Results:RNA-seq technology detected 3329 up-regulated DEGs and 1328down-regulated DEGs.Enrichment analysis found that DEGs in EC samples mainly play a role in regulating the cell cycle and apoptosis process,and the main signal transduction pathway involved is the PI3K-Akt pathway.PPI network screened out 20 core genes,and preliminarily verified CDH1,BUB1 B,MMP9 and FOXM1 as core differential genes by immunohistochemical methods.Conclusion:CDH1,BUB1 B,MMP9 and FOXM1 are important biomarkers for many malignant tumors.Our findings are conducive to further improving the molecular classification of endometrial cancer.