Screening Of Biomarkers For Ovarian Cancer And Analysising Related Mechanisms Based On Clinical Data And Bioinformatics

Purpose:Ovarian cancer(OC)is a common tumor of the female reproductive system,and its fatality rate ranks first among gynecological malignancies.Ovarian tissue structure and composition are complex,and the histological types of primary tumors are various,among which epithelial ovarian cancer(EOC)accounts for 60-90%.The onset of EOC is hidden,and the early symptoms are not obvious.Most patients are in the late stage when they see the doctor,and the prognosis is extremely poor.Therefore,early detection of EOC is the key to improving the prognosis.This study aims to explore the clinical characteristics of EOC,analyze the prognostic factors of EOC,and explore potential biomarkers from two aspects:hematological indicators and key gene screening.Methods:In the first part,we selected 282 patients with epithelial ovarian cancer diagnosed as epithelial ovarian cancer based on pathology from January 1,2007 to December 31,2018 in Suzhou Hospital of Nanjing Medical University.Retrospectively analyze the clinical characteristics and survival of all patients.Kaplan-Meier method was used for survival analysis,log-rank test was used for comparison between groups,and COX regression was used for multivariate analysis.The survival curve was drawn using GraphPad Prism5 software.In the second part,we used a series of bioinformatics methods to find differentially expressed genes(DEGs)and key(HUB)genes,and performed gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional analysis to establish DEGs Protein-protein interaction(PPI)network.Then,in order to further verify the expression of CDC20 in ovarian cancer,4 data sets in the Oncomine database were used to analyze the difference between the cancer tissue and the control group.And analyze the following three aspects in the TCGA database:CDC20 expression differences in cancer tissues and normal tissues,CDC20 expression levels in different ovarian cancer histopathological types and tumor grades.Finally,use the cBioPortal online platform to analyze the disease-free survival of the CDC20 gene.In the third part,after bioinformatics screening,we found that cyclin 20(CDC20)is a key gene of ovarian cancer.Short hairpin RNA(shRNA)was used to silence the CDC20 gene to study its effects on the proliferation,apoptosis of ovarian cancer cells and expression of SRY-related HMG-box gene2(SOX2).Results:In the first part,the results of multivariate COX regression analysis showed that whether fallopian tube ligation,FIGO staging,chemotherapy,chemotherapy resistance,and IBIL level(<6.75 vs≥6.75μmol/L)are independent influencing factors of OS in EOC patients(P<0.05).PFS analysis by the same method showed that whether fallopian tube ligation,FIGO staging,early or late tumor,chemotherapy,chemotherapy resistance,and IBIL level(<6.75 vs≥6.75μmol/L)were the influencing factors of PFS in EOC patients(P<0.05)).In the second part,we found that DEGs are mainly enriched in cell cycle signaling pathway,cancer pathway,progesterone-mediated oocyte maturation,Wnt signaling pathway and P53 signaling pathway.As a key gene,CDC20 is highly expressed in ovarian cancer tissues,and is closely related to ovarian cancer tissue types and tumor grades.Compared with ovarian clear cell carcinoma,ovarian endometrioid carcinoma and mucinous adenocarcinoma,the expression level of CDC20 in serous adenocarcinoma is higher,and the higher the tumor grade,the higher the level of CDC20 expression.CDC20 is related to the prognosis of patients with ovarian cancer,and the prognosis of abnormal expression is poor.In the third part,the experimental results showed that the proliferation rate of ovarian cancer cells decreased and the apoptosis rate increased after silencing the CDC20 gene.The interference effect of CDC20 shRNA02 is the best among the 3 interference shRNAs.CDC20 shRNA02 can reduce the expression of CDC20 at the protein level and downregulate SOX2.Conclusions:This study included 282 patients undergoing epithelial ovarian cancer surgery,and sorted out the age of onset,body mass index(BMI),menopause,number of pregnancy,number of births,number of abortions,history of cesarean section,history of tubal ligation,etc.Symptoms such as abdominal distension,abdominal pain,irregular vaginal bleeding and other general information and surgical pathology and long-term prognosis information.History of tubal ligation,FIGO staging,chemotherapy and drug resistance,and IBIL levels significantly affect the survival of EOC patients,including overall survival and progression-free survival.Preoperative IBIL is a routine liver function test.If it is used clinically,it can effectively save medical costs and has certain clinical application value.The genetically screened CDC20 may be a key biomarker for ovarian cancer.As an upstream regulator of SOX2,it may mediate the SOX2 signaling pathway to regulate the process of ovarian cancer.CDC20 may be used in early detection and prognostic evaluation of ovarian cancer,and become a potential effective treatment target.