WikiPathwaysDec 9, 2023
Identification of necroptosis-related genes for predicting prognosis and exploring immune infiltration landscape in colon adenocarcinoma. https://doi.org/10.3389/fonc.2022.941156 #Tcga #Necroptosis #ColonAdenocarcinoma #PrognosisModel #Immune
Identification of necroptosis-related genes for predicting prognosis and exploring immune infiltration landscape in colon adenocarcinoma

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).Result...

Frontiers
FairfaxLabDec 16, 2022

We replicate the lead #GWAS association for #immunotherapy toxicities at #IL7. We find B cells express IL7 which is induced markedly in #melanoma, w. a bigger effect in risk allele carriers. This signature is associated with B cell maturation. Post treatment, risk allele carriers have increased CD8 T cell cytotoxicity & clonality. Notably, the risk allele is associated with lower progression rates in #TCGA. The work places B cells & IL7 in responses to immunotherapy.

https://www.nature.com/articles/s41591-022-02095-5

IL7 genetic variation and toxicity to immune checkpoint blockade in patients with melanoma - Nature Medicine

Genetic analyses in a cohort of patients with melanoma receiving immunotherapy reveal that variants in IL7 are associated with immune-related adverse events and highlight the role of B cells in mediating toxicity.

Nature