Establishment Of Cervical Cancer Prognosis Model Based On Comprehensive Bioinformatics And The Role Of Hypofolate To Stimulate The Shh/Spp1 Signal Axis To Promote Cervical Cancer Cell Proliferation And Invasion

Objective:1.Analyze the risk factors that affect the progression of CIN1 patients and establish a prediction model;2.Use comprehensive bioinformatics analysis to screen genes related to the prognosis of patients with cervical cancer,construct a prognosis model for patients with cervical cancer,and provide references for subsequent basic experiments;3.Through cell experiments,combined with bioinformatics,verify the molecular mechanism of folic acid in cervical cancer,and provide a theoretical basis for subsequent clinical treatment.Methods:1.By analyzing a cohort study of the research team,using clinical epidemiology to analyze the risk factors that affect the progress of CIN1,and using Nomogram to construct a prognostic score table;2.A comprehensive bioinformatics analysis of cervical cancer based on the GEO,TCGA,and GTEx databases,and a prognostic model of cervical cancer patients was constructed;3.Using PPI network to predict genes related to folic acid and Shh,and use cell proliferation,scratches,and invasion to detect the effect of folic acid on the biological behavior of siha tumor cells;4.Western blot was used to analyze the effect of folic acid on the protein levels of Shh and downstream genes SPP1,and the hypofolate antagonist(5-azacytidine)was used for further verification.Results: 1.HPV,FRα,P16,and serum folic acid can be used as a clinical prediction model for CIN1 disease progression,which is more valuable than HPV alone,and combined with the Nomogram score table,it can quantitatively estimate the prognosis of CIN1 patients;2.Construct central genes that affect cervical cancer,such as KIF20 A,DLGAP5,CDC20,CDK1,KIF11,CCNA2,KIF2 C,TOP2A,BUB1 B,and CCNB2.Using ESTIMATE,it was found that in patients with cervical cancer,immune cells mainly affect the survival time of patients with cervical cancer,and stromal cells have a smaller effect.The multi-gene model of cervical cancer prognosis,the area under the curve of the subject is 0.927,and its risk factor affects the patient’s survival time.Combining age and disease stage can better predict the patient’s prognosis.3.Hypofolate can activate the Hedgehog signaling pathway,increase Shh expression,and affect SPP1,thereby increasing the carcinogenicity of tumor cells.Conclusion:1.Clinical epidemiology can obtain disease-related clinical characteristics and special diagnostic indicators from large samples;2.Bioinformatics can analyze the factors affecting the disease from the perspective of patient genes,and pave the way for mechanism research;3.In vivo experiments can be used as part of basic experiments to verify clinical trials and bioinformatics,and to provide theoretical basis for subsequent clinical practice.