Necroptosis-Related Genes Associated With Immune Activity and Prognosis of Colorectal Cancer

Front Genet. 2022 Jun 16:13:909245. doi: 10.3389/fgene.2022.909245. eCollection 2022.

Abstract

This study aims at screening out the key necroptosis-related genes in colorectal cancer and elucidating the role of necroptosis-related genes in the immune activity and prognosis of colorectal cancer (CRC). The CRC patients' data were downloaded from The Cancer Genome Atlas (TCGA). The non-negative matrix factorization method was applied to identify new molecular subgroups. Survival analysis and single sample Gene Set Enrichment Analysis were performed to determinate the differences in the overall survival time and immune status of the subgroups. Prognostic model was constructed on the basis of univariate Cox regression and LASSO analysis. Functional analyses were used to explore the potential mechanisms. Based on prognostic related necroptosis genes, we identify two molecular subgroups with significantly different survival. The better prognosis was associated with more active immune infiltration and upregulated expression of immune checkpoints. We screened nine necroptosis related genes as key prognostic genes and established a risk model, which showed a good potential for survival prediction in colorectal cancer. Nomogram assessment showed that the model had high reliability for predicting the prognosis of colorectal cancer patients. The high-risk and low-risk group also has different sensitivity to immunotherapy and commonly used drugs for colorectal cancer. Overall, necroptosis related genes were involved in the immune microenvironment of colorectal cancer patient, could be utilized to predict the prognosis of colorectal cancer and develop more individualized treatment.

Keywords: colorectal cancer; drug sensitivity; immune microenvironment; necroptosis; prognostic model.