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

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.

RETRACTED ARTICLE: A novel necroptosis signature for predicting survival in lung adenocarcinoma

“…We acquired necroptosis-related genes (NRGs) from the GSEA (M24779.gmt), KEGG pathway (hsa04217), and previous studies [ 15 , 16 ]. We ultimately identified 204 NRGs in the present study (Table S2 ).…”

Experimental prognostic model integrating N6-methyladenosine-related programmed cell death genes in colorectal cancer

“… 10 , 41 It has been reported that m6A plays an increasingly important role in various physiological and pathological processes in various cancers, 42 including pancreatic cancer, 43 breast cancer, 44 and our published CRC study. 45 While the roles of various programmed cell death (PCD) modes in CRC prognosis have been explored in the literature, these models have primarily focused on individual modes of cell death, such as the apoptosis-related prognostic signature, 46 autophagy-related signature, 47 , 48 , 49 , 50 , 51 cuproptosis-related signature, 52 , 53 , 54 ferroptosis-related signature, 55 , 56 , 57 necroptosis-related signature, 58 , 59 and pyroptosis-related prognostic signature. 60 , 61 , 62 , 63 , 64 , 65 However, the interplay between m6A modification and PCD in CRC prognosis remains unexplored, representing a gap in the existing literature.…”

Differential gene expression of immunity and inflammation genes in colorectal cancer using targeted RNA sequencing

“…Its mechanism is conformable to apoptosis and morphology analogous to necrosis. Necroptosis-related genes are strongly associated with TME of CRC, and patients carrying these gene changes may benefit from immunotherapy and have better prognosis of the disease ( 30 ).…”