共0篇 平均IF=NaN (-)更多分析

    加载中

    logo
    Identification of critical ferroptosis regulators in lung adenocarcinoma that RRM2 facilitates tumor immune infiltration by inhibiting ferroptotic death. Tang Bufu,Xu Wangting,Wang Yajie,Zhu Jinyu,Wang Hailin,Tu Jianfei,Weng Qiaoyou,Kong Chunli,Yang Yang,Qiu Rongfang,Zhao Zhongwei,Xu Min,Ji Jiansong Clinical immunology (Orlando, Fla.) Ferroptosis is a novel form of cell death characterized by heavy iron accumulation and lipid peroxidation that plays a critical role in the tumor microenvironment. However, promising biomarkers associated with tumor immune cell infiltration and the immunotherapy response to ferroptosis regulators remain to be elucidated in lung adenocarcinoma (LUAD) patients. In this study, we defined ferroptosis regulators in LUAD through database analysis and experimental validation to determine the implementation of genes associated with clinical relevance, immunotherapy response and tumor microenvironment in LUAD patients. Multiomics data analysis was performed to explore the CNV features, molecular mechanisms and immunogenic characteristics of ferroptosis regulators in LUAD patients. Then, univariate and multivariate Cox regression analyses were used to identify three genes (DDIT4, RRM2, and SLC2A1) that were closely associated with the prognosis of LUAD patients. The prognostic model based on the determination of these three genes was an independent prognostic factor (p < 0.05, HR = 2.838), and patients with superior predictive performance and higher prognostic risk were more likely to have poor survival rates than those with lower prognostic risk in the training group (p < 0.001, HR = 3.19) and the test group (p < 0.001, HR = 2.94; p < 0.001, HR = 3.44). Activated immune cells, including T helper cells and activated CD8 T cells, were lower in the high-risk group, while type 2 T cells were higher (p < 0.05). Patients with higher prognostic risk were less likely to benefit from immunotherapy, partly due to low CTLA4 levels and an immunosuppressive microenvironment (p < 0.05). Combined with LUAD tissue samples and mouse trials, RRM2 was found to influence lung cancer progression and affect tumor immune cell infiltration. RRM2 inhibition effectively promoted M1 macrophage polarization and suppressed M2 macrophage polarization in vitro and in vivo. And ferroptosis inhibitor ferrostatin-1 treatment effectively re-blanced macrophage polarization mediated by RRM2 inhibition. Taken together, the results of the multiomics data analysis and experimental validation identified ferroptosis regulators as promising biomarkers and therapeutic targets associated with tumor immune infiltration in LUAD patients. 10.1016/j.clim.2021.108872
    Development and Validation of a Novel Ferroptosis-Related Gene Signature for Predicting Prognosis and the Immune Microenvironment in Gastric Cancer. Wang Feng,Chen Cheng,Chen Wei-Peng,Li Zu-Ling,Cheng Hui BioMed research international Ferroptosis is a mode of regulated cell death that depends on iron and plays pivotal roles in regulating various biological processes in human cancers. However, the role of ferroptosis in gastric cancer (GC) remains unclear. In our study, a total of 2721 differentially expressed genes (DEGs) were filtered based on The Cancer Genome Atlas (TCGA) ( = 375) dataset. Weighted gene coexpression network (WGCNA) analysis was then used and identified 7 modules, of which the blue module with the most significant enrichment result was selected. By taking the intersections of the blue module and ferroptosis-related genes (FRGs), we obtained 23 common genes. Functional analysis was performed to explore the biological function of the genes of interest, and with univariate Cox regression (UCR) analysis, survival genes were screened to construct a prognostic model based on 3 genes (SLC1A5, ANGPTL4, and CGAS), which could play a role in predicting the survival of GC patients. UCR and multivariate Cox regression (MCR) analysis revealed that the prognostic index could be used as an independent prognostic indicator and validated using another GSE84437 dataset. Notably, patients in the high-risk group had higher mutation frequencies, such as TTN and TP53. TIMER analysis demonstrated that the risk score strongly correlated with macrophage and CD4+ T cell infiltration. In addition, the high- and low-risk groups illustrated different distributions of different immune statuses. Furthermore, the low-risk group had a higher immunophenoscore (IPS), which meant a better response to immune checkpoint inhibitors (ICIs). Finally, gene set enrichment analysis (GSEA) revealed several significant pathways involved in GC. In this study, a novel FRG signature was built that could predict GC prognosis and reflect the status of the tumor immune microenvironment. 10.1155/2021/6014202
    Metabolic regulation of ferroptosis in the tumor microenvironment. The Journal of biological chemistry Ferroptosis is an iron-dependent, nonapoptotic form of regulated cell death triggered by impaired redox and antioxidant machinery and propagated by the accumulation of toxic lipid peroxides. A compendium of experimental studies suggests that ferroptosis is tumor-suppressive. Sensitivity or resistance to ferroptosis can be regulated by cell-autonomous and non-cell-autonomous metabolic mechanisms. This includes a role for ferroptosis that extends beyond the tumor cells themselves, mediated by components of the tumor microenvironment, including T cells and other immune cells. Herein, we review the intrinsic and extrinsic factors that promote the sensitivity of cancer cells to ferroptosis and conclude by describing approaches to harness the full utility of ferroptotic agents as therapeutic options for cancer therapy. 10.1016/j.jbc.2022.101617
    Evaluation of Ferroptosis-related Gene as a Novel Biomarker Associated with the Immune Microenvironment and Prognosis in Breast Cancer. International journal of general medicine BACKGROUND:Ferroptosis is the latest-discovered, iron-dependent form of regulated cell death. It has been increasingly recognized that ferroptosis-related genes participate in oncogenesis and development of cancers, including breast cancer (). Thus, It is important to explore the biofunctions of ferroptosis-related genes in . METHODS:Transcriptome microarray datasets (GSE22358, GSE9014 and GSE8977, GSE2990 and GSE2034) and TCGA- were retrieved for analyses. And a variety of computational tools were used to identify the roles and associated biological functions in . RESULTS:Two ferroptosis-related genes ( and ) were significantly expressed in GSE22358, GSE9014 and GSE8977. Higher expression of was related with favorable prognosis. TCGA- further confirmed the expression of and the prognostic value of . Co-expression analyses showed the most enriched GO term and KEGG pathways were termination of DNA-templated transcription and Fanconi anemia pathway. Subsequently, immunological analyses showed was significantly associated with various immune infiltration cells; among these, dendritic cells, neutrophils, macrophages were the top three infiltrating cells. Furthermore, was also associated with multiple immunostimulatory molecules and chemokines, including PD-1, PD-L1, CTLA4, B7-H3, VSIR, IL-6, BTLA, CXCL2, and CCR7. These results indicated the potential roles of in the immune reaction during the pathogenesis of breast cancer. CONCLUSION:This study firstly demonstrated that ferroptosis-related gene, , could be associated with immune microenvironment, thereby influencing the development and prognosis of patient with breast cancer. 10.2147/IJGM.S329031
    A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer. Zhang Kaiming,Ping Liqin,Du Tian,Liang Gehao,Huang Yun,Li Zhiling,Deng Rong,Tang Jun Frontiers in molecular biosciences Ferroptosis, a regulated cell death which is driven by the iron-dependent peroxidation of lipids, plays an important role in cancer. However, studies about ferroptosis-related Long non-coding RNAs (lncRNAs) in breast cancer (BC) are limited. Besides, the prognostic role of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer remain unclear. This study aimed to explore the potential prognostic value of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer. RNA-sequencing data of female breast cancer patients were downloaded from TCGA database. 937 patients were randomly separated into training or validation cohort in 2:1 ratio. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 239 reported ferroptosis-related genes. A ferroptosis-related lncRNAs signature was constructed with univariate and multivariate Cox regression analyses in the training cohort, and its prognostic value was further tested in the validation cohort. An 8-ferroptosis-related-lncRNAs signature was developed by multivariate Cox regression analysis to divide patients into two risk groups. Patients in the high-risk group had worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed the risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The area under time-dependent ROC curve (AUC) reached 0.853 at 1 year, 0.802 at 2 years, 0.740 at 5 years in the training cohort and 0.791 at 1 year, 0.778 at 2 years, 0.722 at 5 years in the validation cohort. Further analysis demonstrated that immune-related pathways were significantly enriched in the high-risk group. Analysis of the immune cell infiltration landscape showed that breast cancer in the high-risk group tended be immunologically "cold". We identified a novel ferroptosis-related lncRNA signature which could precisely predict the prognosis of breast cancer patients. Ferroptosis-related lncRNAs may have a potential role in the process of anti-tumor immunity and serve as therapeutic targets for breast cancer. 10.3389/fmolb.2021.678877