scholarly journals Using RNA-Seq to Investigate Immune-Metabolism Features in Immunocompromised Patients With Sepsis

2021 ◽  
Vol 8 ◽  
Author(s):  
Po-Liang Cheng ◽  
Hsin-Hua Chen ◽  
Yu-Han Jiang ◽  
Tzu-Hung Hsiao ◽  
Chen-Yu Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Differentially Expressed Genes ◽  
Cell Function ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Immunocompromised Patients ◽  
Rna Seq ◽  
Cell Repertoire ◽  
Tertiary Referral Centre ◽  
Immunocompetent Patients

Objective: Sepsis is life threatening and leads to complex inflammation in patients with immunocompromised conditions, such as cancer, and receiving immunosuppressants for autoimmune diseases and organ transplant recipients. Increasing evidence has shown that RNA-Sequencing (RNA-Seq) can be used to define subendotype in patients with sepsis; therefore, we aim to use RNA-Seq to identify transcriptomic features among immunocompromised patients with sepsis.Methods: We enrolled patients who were admitted to medical intensive care units (ICUs) for sepsis at a tertiary referral centre in central Taiwan. Whole blood on day-1 and day-8 was obtained for RNA-Seq. We used Gene Set Enrichment Analysis (GSEA) to identify the enriched pathway of day-8/day-1 differentially expressed genes and MiXCR to determine the diversity of T cell repertoire.Results: A total of 18 immunocompromised subjects with sepsis and 18 sequential organ failure assessment (SOFA) score-matched immunocompetent control subjects were enrolled. The ventilator-day, ICU-stay, and hospital-day were similar between the two groups, whereas the hospital mortality was higher in immunocompromised patients than those in immunocompetent patients (50.0 vs. 5.6%, p < 0.01). We found that the top day-8/day-1 upregulated genes in the immunocompetent group were mainly innate immunity and inflammation relevant genes, namely, PRSS33, HDC, ALOX15, FCER1A, and OLR1, whereas a blunted day-8/day-1 dynamic transcriptome was found among immunocompromised patients with septic. Functional pathway analyses of day-8/day-1 differentially expressed genes identified the upregulated functional biogenesis and T cell-associated pathways in immunocompetent patients recovered from sepsis, whereas merely downregulated metabolism-associated pathways were found in immunocompromised patients with septic. Moreover, we used MiXCR to identify a higher diversity of T cell receptor (TCR) in immunocompetent patients both on day-1 and on day-8 than those in immunocompromised patients.Conclusions: Using RNA-Seq, we found compromised T cell function, altered metabolic signalling, and decreased T cell diversity among immunocompromised patients with septic, and more mechanistic studies are warranted to elucidate the underlying mechanism.

scholarly journals Bioinformatics-based Screening of Key Genes for Saponin Metabolism in Quinoa

2021 ◽  
Author(s):  
Chengang Guo ◽  
Zhimin wei ◽  
Wei Lyu ◽  
Yanlou Geng
Keyword(s):  
Differentially Expressed Genes ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Hierarchical Cluster ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Differential Analysis ◽  
Rna Seq ◽  
Protein Coding ◽  
Key Genes

Abstract Quinoa saponins have complex, diverse and evident physiologic activities. However, the key regulatory genes for quinoa saponin metabolism are not yet well studied. The purpose of this study was to explore genes closely related to quinoa saponin metabolism. In this study, the significantly differentially expressed genes in yellow quinoa were firstly screened based on RNA-seq technology. Then, the key genes for saponin metabolism were selected by gene set enrichment analysis (GSEA) and principal component analysis (PCA) statistical methods. Finally, the specificity of the key genes was verified by hierarchical clustering. The results of differential analysis showed that 1654 differentially expressed genes were achieved after pseudogenes deletion. Therein, there were 142 long non-coding genes and 1512 protein-coding genes. Based on GSEA analysis, 116 key candidate genes were found to be significantly correlated with quinoa saponin metabolism. Through PCA dimension reduction analysis, 57 key genes were finally obtained. Hierarchical cluster analysis further demonstrated that these key genes can clearly separate the four groups of samples. The present results could provide references for the breeding of sweet quinoa and would be helpful for the rational utilization of quinoa saponins.

scholarly journals Towards Understanding & Uncovering New Key Players in T-Cell Development upon Aging

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2482-2482
Author(s):  
Hanane Boukarabila ◽  
Kalpana Nattamai ◽  
Medhanie Assmelash Mulaw ◽  
Hartmut Geiger
Keyword(s):  
T Cells ◽  
T Cell ◽  
Differentially Expressed Genes ◽  
T Cell Development ◽  
Cell Lineage ◽  
Cell Development ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Thymic Involution ◽  
Total P

Aging-associated immune remodeling (AAIR) leads to an impaired ability to respond to vaccination and combat infections, and is due to many factors acting in concert. Several studies have linked the T-cell decline that occurs with age to thymic involution. However, there is novel and mounting evidence that also aged lymphoid-primed multipotent progenitors (LMPPs) are immune system intrinsic players in AAIR. However, very little is known on molecular and cellular mechanisms by which aging LMPPs could drive this AAIR phenomenon. Deciphering the underlying mechanisms is of crucial importance for developing new therapies to attenuate AAIR. Here, we present new data demonstrating the dysregulated pathways associated with aged LMPPs and the cellular changes in early thymic differentiation events in driving AAIR. To assess the T-lineage potential of aged LMPPs, we performed single cells ex-vivo OP9D assays using LMPPs (Lin-cKit+Sca1+CD34-Flt3hi) from aged (18-20 month-old) and young (8-10 week-old) C57BL/6 animals as controls. The frequencies of T-cell lineage potential in aged LMPPs and young LMPPs at the single cell level were very similar. This result was also validated in vivo by transplantation assays where 5000 aged or young LMPPs were injected into sub-lethally irradiated young recipients followed by T-cell lineage (CD4+ & CD8+) analysis in the peripheral blood (PB) at 4 weeks post transplantation (Mean; Y:12,75 vs A:16:23 % of total, p=0.46). However, aged LMPPs were associated with a dramatic disadvantage of PB T-cells at 4 weeks post injections (Mean; Y:9 vs A:2.3 % of total, p<0.0001) and in the development of all thymic stages of thymocytes, from early double negative stage CD4-CD8-(DN1) (Mean; Y:30 vs A:8 % of parent, p<0.0001) to double positive stage CD4+CD8+(DP) (Mean; Y:53 vs A:15 % of parent, p<0.0001), as well as single positive (SP) CD4+(Mean; Y:54 vs A:13 % of parent, p<0.0001) and CD8+(Mean; Y:45 vs A:10 % of parent, p<0.0001) thymocytes when intravenously transplanted in combination with 1:1 ratio of young LMPPs into young recipients. To overcome a potential homing to the thymus bias of aged LMPPs in competitive transplants, we performed intra-thymic injections of young and aged LMPPs with identical ratios into sub-lethally irradiated young recipients. The analysis of PB at 4 weeks post injections show a dramatic reduction of PB T-cells derived from aged LMPPs in comparison with young LMPPs (Mean; Y:14.8 vs A:8 % of total, p<0.0001). There was primarily a strong disadvantage towards generating DP stage (Mean; Y:46 vs A:28 % of parent, p<0.0001), suggesting that the intra-thymic injections indeed alleviated the dramatic decrease in the early thymocyte stage DN1 (Mean; Y:31 vs A:22 % of parent, p<0.05). This suggests that aged LMPPs confer a T-cell differentiation and maybe an additional homing to the thymus defect. We also performed RNA-Seq analyses on LMPPs from young and aged mice. Unsupervised hierarchical clustering of differentially expressed genes between young and aged LMPPs highlighted a clear dysregulation of only a few pathways that are involved in T-cell development such as Notch signaling. We next correlated our RNA-Seq data with other immunological signatures in attempt to look for more T-cell specific key factors that are differentially expressed between young and aged LMPPs. Importantly, the results show that the data from our RNA-Seq correlated with more than 400 immunological signatures among which 25 were most highly correlated. Interestingly, this correlation has allowed us to curate a list of the top 30 differentially expressed genes between young and aged LMPPs including T-cell specific transcription factors such as Satb1 and Foxo1. Altogether, our findings reveal that the T-cell immune decline that occurs with age is already imprinted in LMPPs within the bone marrow and translates into a dysregulation of signaling pathways that are directly related to T-cell development. Targeting these pathways could open up new perspectives in attenuating AAIR. Disclosures No relevant conflicts of interest to declare.

scholarly journals C3aR1 Correlates With Immune Cell Infiltration and Serves as Prognostic and Therapeutic Biomarker in Gastric Cancer

2021 ◽  
Author(s):  
weifeng liu ◽  
Zhijie Chu ◽  
Cheng Yang ◽  
Tianbao Yang ◽  
Yanhui Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cell ◽  
Differentially Expressed Genes ◽  
Tumor Tissue ◽  
Immune Cell ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Expression Levels

Abstract As the fourth most common malignancy worldwide, gastric cancer can lead more than 720 000 patient death every year. Precisely therapeutic intervention can significantly improve patients’ survival status underlying the precise clarification by molecular indexes. Identifying the biomarkers highly associated with disease prognosis will be helpful to guide the clinical therapy. C3ar1 is an essential receptor in the complement system, and participates in various biological processes associated with immunological responses. To identify the crucial roles of C3AR1 in gastric cancer tmorigenesis, we determined the mRNA profile, protein expression levels and the clinicopathological indexes using cBioportal, Kaplan-Meier plotter and the Human Protein Atlas databases. To identify the molecular network in C3AR1-expressed gastric cancer, we obtained the differentially expressed genes using the GEPIA database compared with normal stomach tissues. Furthermore, we analyzed the biological impact of these differentially expressed genes using protein-protein interaction network and gene set enrichment analysis, in which we identified the hub genes and critical pathways influenced by over-expressed C3AR1 in gastric cancer. Finally, we evaluated the correlation between the C3AR1 expression levels and immune cell infiltration levels utilizing the Tumor Immunoassay Resource database. Our results revealed that the higher expression level of C3AR1 can lead higher infiltration of T cell CD8+, T cell CD4+, macrophage, neutrophil, B cell and myeloid dendritic cells into tumor tissue. Moreover, we also found that higher infiltration of macrophage cells into tumor tissue can worsen the survival of patients with gastric cancer, which may be highly associated with the polarization states of macrophages (TAM and M2 status). Our investigation suggest that C3AR1 can be as an efficient diagnostic biomarkers for gastric cancer therapy.

scholarly journals Autophagy Regulatory Genes MET and RIPK2 Play a Prognostic Role in Pancreatic Ductal Adenocarcinoma: A Bioinformatic Analysis Based on GEO and TCGA

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Xingyu Li ◽  
Zhiqiang Li ◽  
Hongwei Zhu ◽  
Xiao Yu
Keyword(s):  
Single Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Differentially Expressed Genes ◽  
Clinical Application ◽  
Regulatory Genes ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Ductal Adenocarcinoma ◽  
Rna Seq

Pancreatic ductal adenocarcinoma is a common malignant tumor with a poor prognosis. Autophagy activity changes in both cancer cells and microenvironment and affects the progression of pancreatic ductal adenocarcinoma. The purpose of this study was to predict the prognostic autophagy regulatory genes and their role in the regulation of autophagy in pancreatic ductal adenocarcinoma. We draw conclusions based on gene expression data from different platforms: GSE62165 and GSE85916 from the array platform, TCGA from the bulk RNA-seq platform, and GSE111672 from the single-cell RNA-seq platform. At first, we detected differentially expressed genes in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue based on GSE62165. Then, we screened prognostic genes based on GSE85916 and TCGA. Furthermore, we constructed a risk signature composed of the prognostic differentially expressed genes. Finally, we predicted the probable role of these genes in regulating autophagy and the types of cell expressing these genes. According to our screening criteria, there were only two genes: MET and RIPK2, selected into the development of the risk signature. However, evaluated by log-rank tests, receiver operating characteristic curves, and calibration curves, the risk signature was worth considering its clinical application because of good sensitivity, specificity, and stability. Besides, we predicted that both MET and RIPK2 promote autophagy in pancreatic ductal adenocarcinoma by gene set enrichment analysis. Analysis of single-cell RNA-seq data from GSE111672 revealed that both MET and RIPK2 were expressed in cancer cells while RIPK2 was also expressed in monocytes and neutrophils. After comprehensive analysis, we found that both MET and RIPK2 are related to the prognosis of pancreatic ductal adenocarcinoma and provided some associated clues for clinical application and basic experiment research.

611 RNA-sequencing reveals a unique immune transcriptional landscape in the vaccine sites of patients with circulating T-cell responses to cancer immunization

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A646-A647
Author(s):  
Max Meneveau ◽  
Pankaj Kumar ◽  
Kevin Lynch ◽  
Karlyn Pollack ◽  
Craig Slingluff
Keyword(s):  
T Cell ◽  
Differentially Expressed Genes ◽  
T Cell Responses ◽  
Differentially Expressed ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Cell Responses ◽  
Vaccine Site ◽  
And Control ◽  
Transcriptional Landscape

BackgroundVaccines are a promising therapeutic for patients with advanced cancer, but achieving robust T-cell responses remains a challenge. Melanoma-associated antigen-A3 (MAGE-A3) in combination with adjuvant AS15 (a formulation of Toll-Like-Receptor (TLR)-4 and 9 agonists and a saponin), induced systemic CD4+ T-cell responses in 50% of patients when given subcutaneously/intradermally. Little is known about the transcriptional landscape of the vaccine-site microenvironment (VSME) of patients with systemic T-cell responses versus those without. We hypothesized that patients with systemic T-cell responses to vaccination would exhibit increased immune activation in the VSME, higher dendritic cell (DC) activation/maturation, TLR-pathway activation, and enhanced Th1 signatures.MethodsBiopsies of the VSME were obtained from participants on the Mel55 clinical trial (NCT01425749) who were immunized with MAGE-A3/AS15. Biopsies were taken 8 days after immunization. T-cell response to MAGE-A3 was assessed in PBMC after in-vitro stimulation with recMAGE-A3, by IFNγ ELISPOT assay. Gene expression was assessed by RNAseq using DESeq2. Comparisons were made between immune-responders (IR), non-responders (NR), and normal skin controls. FDR p<0.01 was considered significant.ResultsFour IR, four NR, and three controls were evaluated. The 500 most variable genes were used for principal component analysis (PCA). Two IR samples were identified as outliers on PCA and excluded from further analysis. There were 882 differentially expressed genes (DEGs) in the IR group vs the NR group (figure 1A). Unsupervised clustering of the top 500 DEGs revealed clustering according to the experimental groups (figure 1B). Of the 10 most highly upregulated DEGs, 9 were immune-related (figure 1C). Gene-set enrichment analysis revealed that immune-related pathways were highly enriched in IRs vs NRs (figure 1D). CD4 and CD8 expression did not differ between IR and NR (figure 2A), though both were higher in IR compared to control. Markers of DC activation/maturation were higher in IR vs NR (figure 2B), as were several Th1 associated genes (figure 2C). Interestingly, markers of exhaustion were higher in IR v NR (figure 2D). Expression of numerous TLR-pathway genes was higher in IR vs NR, including MYD88, but not TICAM1 (figure 2E).Abstract 611 Figure 1Gene expression profiling of vaccine site samples from patients immunized with MAGE-A3/AS15. (A) Volcano plots showing the distribution of differentially expressed genes (DEGs) between immune responders (IR) and non-responders (NR), IR and control, and NR and control. (B) Heatmap of the top 500 most differentially expressed genes demonstrating hierarchical clustering of sequenced samples according to IR, NR, and control. (C) Table showing the 10 most highly up and down-regulated genes in IR compared to NR. 9 of the top 10 most highly up-regulated genes are related to the immune response. (D) Enrichment plots from a gene set enrichment analysis highlighting the upregulation of immune related pathways in IR compared to NR. Gene set enrichment data was generated from the Reactome gene set database and included all expressed genes. Significance was set at FDR p <0.01Abstract 611 Figure 2Expression of T-cell markers in IR vs NR vs Control samples in the vaccine site microenvironment (VSME). (A) T-cell markers showing similar expression in IR vs NR but higher expression in IR vs control. (B) Markers of dendritic cell activation and maturation in the VSME which are higher in IR vs control but not IR vs NR. (B) Transcription factors and genes associated with Th1/Th2 responses within the VSME. (D) Genes associated with T-cell exhaustion at the VSME. (E) Expression of TLR pathway genes in the VSME. Expression data is provided in terms of normalized counts. Bars demonstrate median and interquartile range. N=9. IR = immune responder, NR = non-responder, TLR = Toll-like Receptor. * = <0.01, ** < 0.001, *** <0.0001, **** < 0.00001ConclusionsThese findings suggest a unique immune-transcriptional landscape in the VSME is associated with circulating T-cell responses to immunization, with differences in DC activation/maturation, Th1 response, and TLR signaling. Thus, immunologic changes in the VSME are useful predictors of systemic immune response, and host factors that modulate immune-related signaling at the vaccine site may have concordant systemic effects on promoting or limiting immune responses to vaccines.Trial RegistrationSamples for this work were collected from patients enrolled on the Mel55 clinical trial NCT01425749.Ethics ApprovalThis work was completed after approval from the UVA institutional review board IRB-HSR# 15398.

scholarly journals Neuromuscular junction-specific genes screening by deep RNA-seq analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiankun Hui ◽  
Hongyang Jing ◽  
Xinsheng Lai
Keyword(s):  
Ion Channel ◽  
Neuromuscular Junctions ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Muscle Membrane ◽  
Receptor Interaction ◽  
Specific Gene ◽  
Rna Seq ◽  
Channel Activity ◽  
Ppi Networks

Abstract Background Neuromuscular junctions (NMJs) are chemical synapses formed between motor neurons and skeletal muscle fibers and are essential for controlling muscle contraction. NMJ dysfunction causes motor disorders, muscle wasting, and even breathing difficulties. Increasing evidence suggests that many NMJ disorders are closely related to alterations in specific gene products that are highly concentrated in the synaptic region of the muscle. However, many of these proteins are still undiscovered. Thus, screening for NMJ-specific proteins is essential for studying NMJ and the pathogenesis of NMJ diseases. Results In this study, synaptic regions (SRs) and nonsynaptic regions (NSRs) of diaphragm samples from newborn (P0) and adult (3-month-old) mice were used for RNA-seq. A total of 92 and 182 genes were identified as differentially expressed between the SR and NSR in newborn and adult mice, respectively. Meanwhile, a total of 1563 genes were identified as differentially expressed between the newborn SR and adult SR. Gene Ontology (GO) enrichment analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA) of the DEGs were performed. Protein–protein interaction (PPI) networks were constructed using STRING and Cytoscape. Further analysis identified some novel proteins and pathways that may be important for NMJ development, maintenance and maturation. Specifically, Sv2b, Ptgir, Gabrb3, P2rx3, Dlgap1 and Rims1 may play roles in NMJ development. Hcn1 may localize to the muscle membrane to regulate NMJ maintenance. Trim63, Fbxo32 and several Asb family proteins may regulate muscle developmental-related processes. Conclusion Here, we present a complete dataset describing the spatiotemporal transcriptome changes in synaptic genes and important synaptic pathways. The neuronal projection-related pathway, ion channel activity and neuroactive ligand-receptor interaction pathway are important for NMJ development. The myelination and voltage-gated ion channel activity pathway may be important for NMJ maintenance. These data will facilitate the understanding of the molecular mechanisms underlying the development and maintenance of NMJ and the pathogenesis of NMJ disorders.

scholarly journals Transcriptional survey of alveolar macrophages in a murine model of chronic granulomatous inflammation reveals common themes with human sarcoidosis

2018 ◽  
Vol 314 (4) ◽  
pp. L617-L625 ◽  
Author(s):  
Arjun Mohan ◽  
Anagha Malur ◽  
Matthew McPeek ◽  
Barbara P. Barna ◽  
Lynn M. Schnapp ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Murine Model ◽  
Alveolar Macrophages ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Multiwall Carbon Nanotube ◽  
Gene Set Enrichment ◽  
Integrated Network ◽  
Gene Set ◽  
Gene Sets

To advance our understanding of the pathobiology of sarcoidosis, we developed a multiwall carbon nanotube (MWCNT)-based murine model that shows marked histological and inflammatory signal similarities to this disease. In this study, we compared the alveolar macrophage transcriptional signatures of our animal model with human sarcoidosis to identify overlapping molecular programs. Whole genome microarrays were used to assess gene expression of alveolar macrophages in six MWCNT-exposed and six control animals. The results were compared with the transcriptional profiles of alveolar immune cells in 15 sarcoidosis patients and 12 healthy humans. Rigorous statistical methods were used to identify differentially expressed genes. To better elucidate activated pathways, integrated network and gene set enrichment analysis (GSEA) was performed. We identified over 1,000 differentially expressed between control and MWCNT mice. Gene ontology functional analysis showed overrepresentation of processes primarily involved in immunity and inflammation in MCWNT mice. Applying GSEA to both mouse and human samples revealed upregulation of 92 gene sets in MWCNT mice and 142 gene sets in sarcoidosis patients. Commonly activated pathways in both MWCNT mice and sarcoidosis included adaptive immunity, T-cell signaling, IL-12/IL-17 signaling, and oxidative phosphorylation. Differences in gene set enrichment between MWCNT mice and sarcoidosis patients were also observed. We applied network analysis to differentially expressed genes common between the MWCNT model and sarcoidosis to identify key drivers of disease. In conclusion, an integrated network and transcriptomics approach revealed substantial functional similarities between a murine model and human sarcoidosis particularly with respect to activation of immune-specific pathways.

scholarly journals HIV-1 Infection Transcriptomics: Meta-Analysis of CD4+ T Cells Gene Expression Profiles

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 244 ◽  
Author(s):  
Antonio Victor Campos Coelho ◽  
Rossella Gratton ◽  
João Paulo Britto de Melo ◽  
José Leandro Andrade-Santos ◽  
Rafael Lima Guimarães ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Differentially Expressed Genes ◽  
Cd4 T Cells ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Infected Cells ◽  
Hiv 1

HIV-1 infection elicits a complex dynamic of the expression various host genes. High throughput sequencing added an expressive amount of information regarding HIV-1 infections and pathogenesis. RNA sequencing (RNA-Seq) is currently the tool of choice to investigate gene expression in a several range of experimental setting. This study aims at performing a meta-analysis of RNA-Seq expression profiles in samples of HIV-1 infected CD4+ T cells compared to uninfected cells to assess consistently differentially expressed genes in the context of HIV-1 infection. We selected two studies (22 samples: 15 experimentally infected and 7 mock-infected). We found 208 differentially expressed genes in infected cells when compared to uninfected/mock-infected cells. This result had moderate overlap when compared to previous studies of HIV-1 infection transcriptomics, but we identified 64 genes already known to interact with HIV-1 according to the HIV-1 Human Interaction Database. A gene ontology (GO) analysis revealed enrichment of several pathways involved in immune response, cell adhesion, cell migration, inflammation, apoptosis, Wnt, Notch and ERK/MAPK signaling.

scholarly journals The role of ferroptosis in breast cancer patients: a comprehensive analysis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zeng-Hong Wu ◽  
Yun Tang ◽  
Hong Yu ◽  
Hua-Dong Li
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Function Analysis ◽  
Cancer Prognosis ◽  
Differentially Expressed ◽  
Immune Checkpoints ◽  
Cell Functions

AbstractBreast cancer (BC) affects the breast tissue and is the second most common cause of mortalities among women. Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular accumulation of reactive oxygen species (ROS). We constructed a prognostic multigene signature based on ferroptosis-associated differentially expressed genes (DEGs). Moreover, we comprehensively analyzed the role of ferroptosis-associated miRNAs, lncRNAs, and immune responses. A total of 259 ferroptosis-related genes were extracted. KEGG function analysis of these genes revealed that they were mainly enriched in the HIF-1 signaling pathway, NOD-like receptor signaling pathway, central carbon metabolism in cancer, and PPAR signaling pathway. Fifteen differentially expressed genes (ALOX15, ALOX15B, ANO6, BRD4, CISD1, DRD5, FLT3, G6PD, IFNG, NGB, NOS2, PROM2, SLC1A4, SLC38A1, and TP63) were selected as independent prognostic factors for BC patients. Moreover, T cell functions, including the CCR score, immune checkpoint, cytolytic activity, HLA, inflammation promotion, para-inflammation, T cell co-stimulation, T cell co-inhibition, and type II INF responses were significantly different between the low-risk and high-risk groups of the TCGA cohort. Immune checkpoints between the two groups revealed that the expressions of PDCD-1 (PD-1), CTLA4, LAG3, TNFSF4/14, TNFRSF4/8/9/14/18/25, and IDO1/2 among others were significantly different. A total of 1185 ferroptosis-related lncRNAs and 219 ferroptosis-related miRNAs were also included in this study. From the online database, we identified novel ferroptosis-related biomarkers for breast cancer prognosis. The findings of this study provide new insights into the development of new reliable and accurate cancer treatment options.

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