Identification of necroptosis-related genes for predicting prognosis and exploring immune infiltration landscape in colon adenocarcinoma

Abstract

BackgroundNecroptosis is a recently discovered form of cell death that plays an important role in the occurrence and development of colon adenocarcinoma (COAD). Our study aimed to construct a risk score model to predict the prognosis of patients with COAD based on necroptosis-related genes.MethodsThe gene expression data of COAD and normal colon samples were obtained from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to calculate the risk score based on prognostic necroptosis-related differentially expressed genes (DEGs). Based on the risk score, patients were classified into high- and low-risk groups. Then, nomogram models were built based on the risk score and clinicopathological features. Otherwise, the model was verified in the Gene Expression Omnibus (GEO) database. Additionally, the tumor microenvironment (TME) and the level of immune infiltration were evaluated by “ESTIMATE” and single-sample gene set enrichment analysis (ssGSEA). Functional enrichment analysis was carried out to explore the potential mechanism of necroptosis in COAD. Finally, the effect of necroptosis on colon cancer cells was explored through CCK8 and transwell assays. The expression of necroptosis-related genes in colon tissues and cells treated with necroptotic inducers (TNFα) and inhibitors (NEC-1) was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe risk score was an independent prognostic risk factor in COAD. The predictive value of the nomogram based on the risk score and clinicopathological features was superior to TNM staging. The effectiveness of the model was well validated in GSE152430. Immune and stromal scores were significantly elevated in the high-risk group. Moreover, necroptosis may influence the prognosis of COAD via influencing the cancer immune response. In in-vitro experiments, the inhibition of necroptosis can promote proliferation and invasion ability. Finally, the differential expression of necroptosis-related genes in 16 paired colon tissues and colon cancer cells was found.ConclusionA novel necroptosis-related gene signature for forecasting the prognosis of COAD has been constructed, which possesses favorable predictive ability and offers ideas for the necroptosis-associated development of COAD.

Identification of colon adenocarcinoma necroptosis subtypes and tumor antigens for the development of mRNA vaccines

“…Zhang et al [ 31 ] reported that PRMT1 inhibited immune escape of colon cancer cells by enhancing RIP3 methylation. In addition, previous studies have shown that many NRGs had potential value in predicting the prognosis of COAD patients [ 32 , 33 ]. Therefore, studying the correlation between necroptosis and immune regulation in COAD can provide new therapeutic strategies for patients with COAD.…”

Procoagulant genes may affect angiogenesis, epithelial-mesenchymal transition, survival prognosis and tumor immune microenvironment in patients with urothelial carcinoma

“…In addition, the important role of coagulation-related factors in bladder cancer has not been reported yet. AGING It has been proved feasible to construct a risk signature with the expression of key genes to monitor the tumor and its microenvironment state [5][6][7]. We divided bladder cancer into two states of hypercoagulability and low coagulation by clustering coagulation-related genes, and we found that hypercoagulability presaged a poor prognosis of bladder tumors.…”