Analyzing Prognostic Effect Of Tumor-hypoxia-related-genes On Colon Adenocarcinoma And Its Mechanism By Bioinformatics

Objective:Colorectal cancer is a common malignant tumor in the gastrointestinal tract,which is one of the diseases with the highest cancer incidence and mortality in the world.,with only 63%5-year overall survival in 2019.More and more studies have shown that in hypoxic microenvironment,some malignancy would undergo adaptive changes,thereby promoting angiogenesis,reprogramming energy metabolism to escape immune disruption,promoting invasion and metastasis.Hence,this study investigated the prognostic effect of hypoxia on colon adenocarcinoma via the public database,and established a risk prediction model,as well as exploring its mechanism.Methods:Firstly,using GSE58049 and TCGA-COAD dataset to identify tumor-hypoxiarelated genes.Then according to univariate regression analysis,Lasso regression analysis and AIC value to screen out those genes with high prognostic value and establish a tumor-hypoxia-related-genes prognostic signature.Based on the risk scores of tumor-hypoxia-related-genes prognostic signature to divide colon adenocarcinoma patients into low-risk and high-risk subgroups,and analyzing their differences,such as the prognosis of survival,clinical characteristics,enrichment and tumor immune cells infiltrating level.In addition,a prognostic model of colon adenocarcinoma was constructed based on the risk score of tumor-hypoxia-related-genes prognostic signature,age and stage.Finally,we further explored the differentially expressed mRNAs and miRNAs between the high and low risk subgroups of tumor-hypoxiarelated-genes prognostic signature through differential analysis,and used target gene prediction network to find their potential target IncRNAs,so as to explore the potential interaction mechanism of mRNA,miRNA and lncRNA colon adenocarcinoma.Results:1.In this study,a total of 307 hypoxia-related genes were screened out and finally retained 10 hypoxia-related genes with high prognostic value to construct a tumor-hypoxia-related-genes prognostic signature.2.There were significant differences between the high-risk subgroup and low-risk subgroup,and the high-risk subgroups enriched in malignancy-associated biological processes,suggesting its prognosis was poor and was further verified by survival analysis.3.A prognostic model was constructed based on the risk score of tumor-hypoxiarelated-genes prognostic signature,age and stage to predict the prognosis of colon adenocarcinoma,and the model had a good prognostic ability.4.In addition,our study inferred a competing endogenous RNAs network(NR2F1AS1/miR-508-3p/SLC6A14)in colon adenocarcinoma,which might influence the level of infiltration of CD8(+)T cells and MO Macrophages,providing a direction for the subsequent functional studies.Conclusion:This study analyzed the tumor-hypoxia-related-genes effect on the prognosis of colon adenocarcinoma,established a tumor hypoxia-related-genes prognostic signature,and constructed a prognostic model with outstanding ability of predicting colon adenocarcinoma prognosis,which had a good ability in predicting the prognosis and could be used to guide the prognostic evaluation of colon adenocarcinoma in clinical practice.In addition,our study speculated that there was an endogenous competitive RNA regulatory network in colon adenocarcinoma,which might affect the infiltrating levels of CD8(+)T cells and M0 macrophages,providing a direction for further research.