Hypoxia Constructing the Prognostic Model of Colorectal Adenocarcinoma and Related to the Immune Microenvironment

Abstract

Background: Hypoxia is a common phenomenon in solid tumors, which plays an important role in tumor proliferation, apoptosis, angiogenesis, invasion and metastasis, energy metabolism and chemoradiotherapy resistance. However, comprehensive analysis of hypoxia markers in colorectal adenocarcinoma (COAD) is still lacking. And there is a need for mechanism exploration and clinical application.Methods: The gene expression, mutation and clinical data of COAD were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. Tumor samples from TCGA were randomly divided into the training and internal validation groups, while tumor samples from GEO were used as the external validation group. Univariate COX—LASSO—multivariate COX method was applied to construct the prognostic model. We clustered all TCGA tumor samples into high, medium and low hypoxia groups, evaluated the correlation between hypoxia degree and immunoactivity, and explored the combined effect of mutation for common target genes and model riskscore on survival in COAD patients. Finally, we developed a dynamic nomograph App online for direct clinical application and carried out multiple validations of the prognostic model.Results: Our hypoxia-related prognostic model for COAD patients is accurate and has been successfully validated internally and externally. Single Sample Gene Set Enrichment Analysis (ssGSEA) and Gene Set Enrichment Analysis (GSEA) results suggest that for COAD patients with higher hypoxia, the stronger the associated immunosuppressive activity, providing a possible mechanism for the lower survival rate. Finally, the dynamic nomograph App online enhances the clinical translational significance of the study.Conclusion: In this study, an accurate prognostic model for COAD patients was established and validated. In addition, our innovative findings include correlations between hypoxia levels and immune activity, as well as an in-depth exploration of common target gene mutations.

A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas

“…In addition, PSMD12 expression is reportedly upregulated in glioma tissues compared with normal brain tissues and positively correlated with glioma grade. Zhang et al (40) constructed a PSMD12-containing prognostic model for hypoxia in colorectal cancer and verified its high accuracy. UBB is a ubiquitin gene, a protein found in eukaryotic cells.…”

“…Zhang et al. ( 40 ) constructed a PSMD12-containing prognostic model for hypoxia in colorectal cancer and verified its high accuracy. UBB is a ubiquitin gene, a protein found in eukaryotic cells.…”

Exploration of Different Hypoxia Patterns and Construction of a Hypoxia-Related Gene Prognostic Index in Colorectal Cancer

“…constructed a prognostic hypoxia model based on five genes. However, the AUC values for 1, 3, and 5 years in their internal validation group were only 0.614, 0.585, and 0.514, respectively ( 45 ). Yang et al.…”

Construction of novel hypoxia-related gene model for prognosis and tumor microenvironment in endometrial carcinoma

“…NK cells are known as the immune cell system’s toxic lymphocytes. According to research, the expression of natural killer group 2 member A (NKG2A) of the NK cell receptor is up-regulated in the peripheral blood of colon cancer patients, and the monitoring and killing capabilities of NK cells are blocked, resulting in the immune escape of colon cancer cells ( 47 ). Patients were also shown to have considerably lower numbers of NK cells than normal participants, which might be a factor in the development of UCEC.…”