The Expression And Clinical Significance Of TYMS Gene In Epithelial Ovarian Cancer By Bioinformatics Combined Tissue Chip Study

Objective:By studying the expression of Thymidylate Synthetase(TYMS)gene in epithelial ovarian cancer(EOC)and its relationship with clinicopathological characteristics,the clinical significance of TYMS gene in EOC and its possible mechanism of action were discussed,which provided the oretical basis for further study.Methods:1.Analysis the 13 studies on the expression of TYMS gene in ovarian cancer in the Oncomine database.The cBioPortal database was used to construct the gene expression network diagram of TYMS gene and its most relevant gene.The Gene Ontology(GO)functional Annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were analyzed in The Database for Annotation,Visualization and Integrated Discovery(DAVID).The TYMS binding sites were mined from the Eukaryotic Promoter Database(EPD).The upstream gene E2F Transcription Factor 3(E2F3)was screened.2.The expression of E2F3 and TYMS in 70 cases of EOC and 10 cases of paracancer tissues in the tissue chip was detected by Immunohistochemistry(IHC).The relationship between the expression of E2F3 and TYMS and the clinicopathological characteristics as well as the correlation between the two were analyzed to investigate the clinical significance of TYMS gene in EOC and its possible mechanism.Results:1.Through mining 13 research data of TYMS gene expression in ovarian cancer from Oncome database,we found that TYMS gene expression was highly expressed in ovarian cancer and the difference was statistically significant(P<0.05).2.The 39 genes closely related to TYMS were obtained using the cBioPortal database.They were ATIC,CCNA1,CCNE1,CDC45A,CDC45,CDC6,CDT1,CSNK2A1,CSNK2A2,DHFR,DHFR2,E2F1,E2F3,FBXO5,GART,MTR,MTRR,ORC1,PCNA,POLA1,POLA2,POLD1,POLD2,POLD3,POLD4,POLE,POLG,POLG2,PRIM1,PRIM2,REV3L,RR M2,SLC25A32,TFDP2,TK1,TK2,16 go functional notes and 58 KEGG pathways were constructed through DAVID database.The main biological function of TYMS gene is to regulate the G1/S-phase transformation of mitotic cells.E2F3 obtained from cBioPortal database is the key factor of Gl/S-phase proliferation regulation.The EPD database showed that there were four possible binding sites of E2F3 in the region-1000-1000 of TYMS gene DNA sequence,suggesting that E2F3 could bind to TYMS and directly regulate TYMS expression.3.The positive rates of E2F3 and TYMS in 70 EOC tissues were 65.71%.58.57%,which were significantly higher than those of 30%and 20%in paracancer tissues(P<0.05).4.The relationship between the expression of E2F3 and TYMS protein and the clinicopathological characteristics of 70 EOC patients was analyzed.It was found that the positive expression rate of E2F3 in the tissues of patients with serous ovarian cancer,federation international of gynecology and Obstetrics(FIGO)stage ?-?.and EOC with lymph node metastasis was higher than that of other types of epithelial cancer,FIGO stage ?-?,and no lymph node metastasis,The difference was statistically significant(P<0.05),but there was no significant difference in the expression of EOC in different tissue differentiation degree and age(P>0.05).The positive expression rate of TYMS in ovarian serous cancer,FIGO ?-?,EOC with lymph node metastasis and poor differentiation was higher than that in other epithelial cancer,FIGO ?-?,EOC without lymph node metastasis and good tissue differentiation(P<0.05);the expression of TYMS in patients under 50 years old and? 50 years old had no statistical significance(P>0.05).5.Pearson correlation analysis showed that there was a positive correlation between the expression TYMS and E2F3 in EOC(R=0.885,P=0.001).Conclusion:1.TYMS gene is significantly overexpressed in EOC,which is related to the progress of EOC.The value of TYMS as a potential biomarker for EOC diagnosis,prognosis prediction and targeted therapy deserves further study.2.E2F3 may regulate cell cycle progression and promote EOC progression by combining with TYMS.moreexperiment in vivo and vitro are needed to verify the mechanism of action in the future.3.Bioinformatics,as a new science,is of great significance to find key genes and potential therapeutic targets in biomedical research.It is time-saving,labor-saving and can reduce blindness.