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Establishment Of Prognostic Model Of Gastric Cancer And Determination Of Tumor Microenvironment Characteristics Based On Oxidative Stress-related Genes

Posted on:2024-06-23Degree:MasterType:Thesis
Country:ChinaCandidate:Z H BaiFull Text:PDF
GTID:2544307148976629Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective:As one of the most common digestive system tumors in my country,gastric cancer has high morbidity and mortality.Oxidative stress is a state in which excessive accumulation of reactive oxygen species in the body disrupts cell homeostasis and is involved in the occurrence of various diseases.However,oxidative stress-related genes(ORGs)and the tumor microenvironment(TME)relationship is currently little research.In order to improve the treatment strategy of gastric cancer,the study of the relationship between the two is extremely necessary.Methods:608 genes related to oxidative stress were obtained through the Amigo database.The gastric cancer transcriptome data and corresponding clinical data were downloaded from the Cancer Genome Atlas(TCGA)official website.Changes in ORGs in 732 gastric cancer samples from two datasets were extracted.By analyzing the copy number variation(CNV)and somatic mutation of ORGs associated with the prognosis of gastric cancer to determine its genetic variation landscape.The gastric cancer subtypes related to ORGs were obtained by unsupervised clustering method,and the differences in TME invasion and clinical characteristics were analyzed.Subsequently,the differentially expressed genes(DEGs)based on the prognosis of the two gastric cancer subtypes,construct the genotyping of gastric cancer patients,and use the Lasso-Cox regression model to establish the risk model(OE_score)related to recurrence-free survival(RFS).And further study whether there is a correlation between OE_score and TME,tumor mutation burden(TMB),microsatellite instability(MSI),immunotherapy,stem cell analysis,chemotherapy drugs,etc.Results:Among the genes related to oxidative stress,there were 48 genes related to the prognosis of gastric cancer.These 48 prognosis-related ORGs had extensive somatic mutations and copy number variations in gastric cancer patients.Gastric cancer subtypes constructed based on prognosis-related ORGs had significant differences in prognosis,gene expression,pathway enrichment analysis,TME infiltration,and clinical features.Then,the molecular subtype constructed by us based on the 593 prognostic DEGs obtained from the two gastric cancer subtypes was also verified to have significant prognostic differences.Finally,the OE_score composed of 7 genes has also been shown to be related to TME,TMB,MSI,immunotherapy,stem cell analysis,and chemotherapy drugs.Conclusion:Based on the method of bioinformatics,this study determined that there are differences in the epigenetic level and gene expression level of ORGs in gastric cancer.It was determined that gastric cancer subtypes and gene subtypes established based on ORGs had significant differences in prognosis and tumor microenvironment.And it is determined that OE_score is related to various features.This suggests that there is a link between oxidative stress and gastric cancer,which can provide new ideas for the treatment and prognosis of gastric cancer.
Keywords/Search Tags:gastric cancer, oxidative stress, tumor microenvironment, prognosis, microsatellite instability
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