Disulfidptosis-based molecular clustering and prognostic signatures predict patient survival and the immune landscape in patients with colon cancerWen, Ma, Li
et alDiscov Oncol (2025) 16 (1), 354
Abstract: Disulfidptosis is a unique type of programmed cell death that is distinct from previously known forms of cell death, such as pyroptosis, apoptosis, and necroptosis. Researchers have studied the significance of many forms of cell death in various diseases, particularly malignant tumors, in great detail in recent years. Therefore, how disulfidptosis affects colon cancer and how it functions in the immune system are unknown.Disulfidptosis-related gene (DRG) expression information was obtained from the TCGA-COAD cohort. Patients were categorized into two DRG groups using consensus cluster analysis, and the disulfidptosis-related differentially expressed genes (DRDEGs) were subsequently identified by differential analysis of the two clusters. Univariate Cox regression analysis of the DRDEGs was used to identify prognosis-related DEGs (PRDEGs). The screened PRDEGs were then subjected to LASSO-Cox regression analysis to determine the prognostic model on the basis of ten genes. Immunohistochemistry was used to verify the expression and prognostic value of marker genes.In the two DRG clusters, the characteristics of the tumor microenvironment (TME) significantly differed by the TME scores and infiltration levels of 23 human immune cell subpopulations. Prognostically meaningful risk scores were found, with a greater chance of mortality (p = 4.4e-7) for patients in the high-risk category. Furthermore, notable differences in TME scores, immune cell infiltration, and immune checkpoint expression were detected among the risk categories. The ROC curves revealed that the nomogram's 1-, 2-, and 3-year AUCs were 0.75, 0.76, and 0.77, respectively, demonstrating the superior predictive capacity of the nomogram. Immunohistochemistry revealed that patients with high FABP4 and low ADAM8 and FSTL3 expressions had a better prognosis.The prognostic features based on 10 PRDEGs performed well in predicting survival, TME status, and response to immunity in COAD patients, helping provide personalized immunotherapy strategies for patients.© 2025. The Author(s).
Exploration of crucial stromal risk genes associated with prognostic significance and chemotherapeutic opportunities in invasive ductal breast carcinomaTang, Wang, Geng
et alJ Genet Eng Biotechnol (2025) 23 (1), 100448
Abstract: Few studies revealed that stromal genes regulate the tumor microenvironment (TME). However, identification of key-risk genes in the invasive ductal breast carcinoma-associated stroma (IDBCS) and their associations with the prediction of risk group remains lacking.This study used the GSE9014, GSE10797, GSE8977, GSE33692, and TGGA BRCA datasets. We explored the differentially expressed transcriptional markers, hub genes, gene modules, and enriched KEGG pathways. We employed a variety of algorithms, such as the log-rank test, the LASSO-cox model, the univariate regression model, and the multivariate regression model, to predict prognostic-risk genes and the prognostic-risk model. Finally, we employed a molecular docking-based study to explore the interaction of sensitive drugs with prognostic-risk genes.In comparing IDBCS and normal stroma, we discovered 1472 upregulated genes and 1400 downregulated genes (combined ES > 0585 and adjusted p-value < 0.05). The hub genes enrich cancer, immunity, and cellular signaling pathways. We explored the 12 key risk genes (ADAM8, CD86, CSRP1, DCTN2, EPHA1, GALNT10, IGFBP6, MIA, MMP11, RBM22, SLC39A4, and SYT2) in the IDBCS to identify the high-risk group and low-risk group patients. The high-risk group had a lower survival rate, and the constructed ROC curves evaluated the validity of the risk model. Expression validation and diagnostic efficacy revealed that the key stromal risk genes are consistently deregulated in the high-risk group and high stromal samples of the TCGA BRCA cohort. The expression of crucial risk genes, including CD86, CSRP1, EPHA1, GALNT10, IGFBP6, MIA, and RBM22 are associated with drug resistance and drug sensitivity. Finally, a molecular docking study explored several sensitive drugs (such as QL-XII-61, THZ-2-49, AZ628, NG-25, lapatinib, dasatinib, SB590885, and dabrafenib) interacted with these essential risk genes through hydrogen bonds and other chemical interactions.Exploring essential prognostic-risk genes and their association with the prognosis, diagnostic efficacy, and risk-group prediction may provide substantial clues for targeting the breast cancer stromal key-risk genes.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Roles of Adam8 in Neuroinflammation in experimental ischemic Stroke: Insights from single-cell and ribosome-bound mRNA sequencingLiu, Xu, Lu
et alExp Neurol (2025) 388, 115207
Abstract: Stroke remains a leading cause of global mortality, with neuroinflammation significantly exacerbating clinical outcomes. Microglia serve as key mediators of post-stroke neuroinflammation, though the mechanisms driving their migration to injury sites remain poorly understood. In this study, using publicly available single-cell sequencing data (GSE234052), we identified a migration-associated microglial subtype in a murine model of distal middle cerebral artery occlusion (dMCAO). Additionally, ribosome-bound mRNA sequencing data (GSE225110) from microglia isolated from peri-infarct cortical tissue uncovered dMCAO-induced alterations in microglial mRNA translation. By integrating these datasets, we identified A Disintegrin And Metalloproteinase 8 (Adam8) as a key gene upregulated at both the transcriptional and translational levels post-dMCAO. Protein analysis revealed that both the precursor and active forms of Adam8 were predominantly expressed in microglia and significantly upregulated in peri-infarct regions following dMCAO. Notably, Adam8 inhibition with BK-1361 significantly reduced Adam8 cleavage, M1 microglial migration, inflammation, infarct size, and improved neurological outcomes. Bioinformatics analysis further identified Myo1e as a potential interacting partner of Adam8, a finding validated through immunofluorescence co-localization. These findings highlight Adam8 as a promising therapeutic target for mitigating post-stroke neuroinflammation and offer new insights into the mechanisms of microglial migration.Copyright © 2025 Elsevier Inc. All rights reserved.
Gene Expression Signatures of Porcine Bone Marrow-Derived Antigen-Presenting Cells Infected with Classical Swine Fever VirusCoronado, Wang, Bohórquez
et alViruses (2025) 17 (2)
Abstract: For a better understanding of classical swine fever (CSF) pathogenesis, a transcriptomic analysis was performed using porcine bone marrow (BM)-derived antigen-presenting cells (APCs) infected ex vivo with two different cDNA-derived classical swine fever virus (CSFV) strains, the low-virulence Pinar de Rio (vPdR-36U) or the lethal vPdR-H30K-5U. The transcriptomic profile of vPdR-36U- or vPdR-H30K-5U-infected versus noninfected cells revealed 946 and 2643 differentially expressed genes (DEGs), respectively. The upregulation of ISG15, CXCL-10, ADAM8, and CSF1 was found after infection with vPdR-36U, which could contribute to the generation of mild CSF forms. In contrast, cells infected with the lethal vPdR-H30K-5U overexpressed the immune checkpoint molecules PD-L1, CD276, and LAG3, which are involved in T-cell exhaustion and could be associated with adaptive immunity impairment. vPdR-H30K-5U also induced increased expression of PPBP, IL-8, IL-6, ECE1, and Rab27b, which are mediators of inflammatory responses that can be involved in cytokine storms. The TNF signaling pathway, which is related to the activation and proliferation of different subsets of immune cells, including CD4+ T cells, was notably upregulated in response to the low-pathogenicity virus. The Th17, Th1, and Th2 differentiation pathways were downregulated by the highly pathogenic virus only, supporting the role of T-cell-mediated immunity in protecting against CSFV.
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