scholarly journals Immunological and prognostic significance of novel ferroptosis-related genes in soft tissue sarcoma

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262234
Author(s):  
Jiazheng Zhao ◽  
Yi Zhao ◽  
Xiaowei Ma ◽  
Helin Feng ◽  
Rongmin Cui
Keyword(s):  
Dendritic Cell ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Immune Cells ◽  
Plasmacytoid Dendritic Cell ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Prognostic Models ◽  
Immune Checkpoints ◽  
Hub Genes

Background Ferroptosis has exhibited great potential in the treatment of cancer and has gained widespread attention in soft tissue sarcoma (STS). The aim was to explore the immunological and prognostic significance of novel ferroptosis-related genes in STS. Methods We identified ferroptosis-related differentially expressed genes (DEGs) in STS to construct the networks of enrichment analysis and protein-protein interaction. Subsequently, hub genes with prognostic significance were localized and a series of prognostic and immune analyses were performed. Results 40 ferroptosis-related DEGs were identified, of which HELLS, STMN1 EPAS1, CXCL2, NQO1, and IL6 were classified as hub genes and were associated with the prognosis in STS patients. In the results of the immune analysis, PDCD1, CTLA4, TIGIT, IDO1 and CD27 exhibited consistent intense correlations as immune checkpoint genes, as well as macrophage, neutrophil, cytotoxic cell, dendritic cell, interdigitating dendritic cell and plasmacytoid dendritic cell as immune cells. EPAS1 and HELLS might be independent prognostic factors for STS patients, and separate prognostic models were constructed by using them. Conclusions We recognized novel ferroptosis-related genes with prognostic value in STS. Furthermore, we searched out potential immune checkpoints and critical immune cells.

scholarly journals Identification of ferroptosis genes in immune infiltration and prognosis in thyroid papillary carcinoma using network analysis

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ruoting Lin ◽  
Conor E. Fogarty ◽  
Bowei Ma ◽  
Hejie Li ◽  
Guoying Ni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Carcinoma ◽  
Risk Score ◽  
Immune Cells ◽  
Survival Curve ◽  
Enrichment Analysis ◽  
Papillary Thyroid ◽  
Hub Genes ◽  
Cox Analysis ◽  
Cluster 2

Abstract Background Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. While many patients survive, a portion of PTC cases display high aggressiveness and even develop into refractory differentiated thyroid carcinoma. This may be alleviated by developing a novel model to predict the risk of recurrence. Ferroptosis is an iron-dependent form of regulated cell death (RCD) driven by lethal accumulation of lipid peroxides, is regulated by a set of genes and shows a variety of metabolic changes. To elucidate whether ferroptosis occurs in PTC, we analyse the gene expression profiles of the disease and established a new model for the correlation. Methods The thyroid carcinoma (THCA) datasets were downloaded from The Cancer Genome Atlas (TCGA), UCSC Xena and MisgDB, and included 502 tumour samples and 56 normal samples. A total of 60 ferroptosis related genes were summarised from MisgDB database. Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) were used to analyse pathways potentially involving PTC subtypes. Single sample GSEA (ssGSEA) algorithm was used to analyse the proportion of 28 types of immune cells in the tumour immune infiltration microenvironment in THCA and the hclust algorithm was used to conduct immune typing according to the proportion of immune cells. Spearman correlation analysis was performed on the ferroptosis gene expression and the correlation between immune infiltrating cells proportion. We established the WGCNA to identify genes modules that are highly correlated with the microenvironment of immune invasion. DEseq2 algorithm was further used for differential analysis of sequencing data to analyse the functions and pathways potentially involving hub genes. GO and KEGG enrichment analysis was performed using Clusterprofiler to explore the clinical efficacy of hub genes. Univariate Cox analysis was performed for hub genes combined with clinical prognostic data, and the results was included for lasso regression and constructed the risk regression model. ROC curve and survival curve were used for evaluating the model. Univariate Cox analysis and multivariate Cox analysis were performed in combination with the clinical data of THCA and the risk score value, the clinical efficacy of the model was further evaluated. Results We identify two subtypes in PTC based on the expression of ferroptosis related genes, with the proportion of cluster 1 significantly higher than cluster 2 in ferroptosis signature genes that are positively associated. The mutations of Braf and Nras are detected as the major mutations of cluster 1 and 2, respectively. Subsequent analyses of TME immune cells infiltration indicated cluster 1 is remarkably richer than cluster 2. The risk score of THCA is in good performance evaluated by ROC curve and survival curve, in conjunction with univariate Cox analysis and multivariate Cox analysis results based on the clinical data shows that the risk score of the proposed model could be used as an independent prognostic indicator to predict the prognosis of patients with papillary thyroid cancer. Conclusions Our study finds seven crucial genes, including Ac008063.2, Apoe, Bcl3, Acap3, Alox5ap, Atxn2l and B2m, and regulation of apoptosis by parathyroid hormone-related proteins significantly associated with ferroptosis and immune cells in PTC, and we construct the risk score model which can be used as an independent prognostic index to predict the prognosis of patients with PTC.

scholarly journals Prognostic and immunological value of LTB4R in pan-cancer

2021 ◽  
Vol 18 (6) ◽  
pp. 9336-9356
Author(s):  
Sidan Long ◽  
◽  
Shuangshuang Ji ◽  
Kunmin Xiao ◽  
Peng Xue ◽  
...  
Keyword(s):  
Immune Cells ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Negative Influence ◽  
Leukotriene B4 ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Significant Difference ◽  
Pan Cancer

<abstract> <sec><title>Background</title><p>LTB4 receptor 1 (LTB4R), as the high affinity leukotriene B4 receptor, is rapidly revealing its function in malignancies. However, it is still uncertain.</p> </sec> <sec><title>Methods</title><p>We investigated the expression pattern and prognostic significance of LTB4R in pan-cancer across different databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter, in this study. Meanwhile, we explored the significance of LTB4R in tumor metastasis by HCMDB. Then functional enrichment analysis of related genes was performed using GeneMANIA and DAVID. Lastly, utilizing the TIMER datasets, we looked into the links between LTB4R expression and immune infiltration in malignancies.</p> </sec> <sec><title>Results</title><p>In general, tumor tissue displayed higher levels of LTB4R expression than normal tissue. Although LTB4R had a negative influence on pan-cancer, a high expression level of LTB4R was protective of LIHC (liver hepatocellular carcinoma) patients' survival. There was no significant difference in the distribution of LTB4R between non-metastatic and metastatic tumors. Based on Gene Set Enrichment Analysis, LTB4R was implicated in pathways involved in inflammation, immunity, metabolism, and cancer diseases. The correlation between immune cells and LTB4R was found to be distinct across cancer types. Furthermore, markers of infiltrating immune cells, such as Treg, T cell exhaustion and T helper cells, exhibited different LTB4R-related immune infiltration patterns.</p> </sec> <sec><title>Conclusion</title><p>The LTB4R is associated with immune infiltrates and can be used as a prognostic biomarker in pan-cancer.</p> </sec> </abstract>

scholarly journals Identification of potential therapeutic targets for atherosclerosis by analysing the gene signature related to different immune cells and immune regulators in atheromatous plaques

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yang Shen ◽  
Li-rong Xu ◽  
Xiao Tang ◽  
Chang-po Lin ◽  
Dong Yan ◽  
...  
Keyword(s):  
Immune Cells ◽  
Plasma Cells ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gamma Delta ◽  
Hub Genes ◽  
Gene Set Enrichment ◽  
Bioinformatics Analyses ◽  
Immune Infiltration ◽  
Atheromatous Plaques

Abstract Background Atherosclerosis is a chronic inflammatory disease that affects multiple arteries. Numerous studies have shown the inherent immune diversity in atheromatous plaques and suggest that the dysfunction of different immune cells plays an important role in atherosclerosis. However, few comprehensive bioinformatics analyses have investigated the potential coordinators that might orchestrate different immune cells to exacerbate atherosclerosis. Methods Immune infiltration of 69 atheromatous plaques from different arterial beds in GSE100927 were explored by single-sample-gene-set enrichment analysis (presented as ssGSEA scores), ESTIMATE algorithm (presented as immune scores) and CIBERSORT algorithm (presented as relative fractions of 22 types of immune cells) to divide these plaques into ImmuneScoreL cluster (of low immune infiltration) and ImmuneScoreH cluster (of high immune infiltration). Subsequently, comprehensive bioinformatics analyses including differentially-expressed-genes (DEGs) analysis, protein–protein interaction networks analysis, hub genes analysis, Gene-Ontology-terms and KEGG pathway enrichment analysis, gene set enrichment analysis, analysis of expression profiles of immune-related genes, correlation analysis between DEGs and hub genes and immune cells were conducted. GSE28829 was analysed to cross-validate the results in GSE100927. Results Immune-related pathways, including interferon-related pathways and PD-1 signalling, were highly enriched in the ImmuneScoreH cluster. HLA-related (except for HLA-DRB6) and immune checkpoint genes (IDO1, PDCD-1, CD274(PD-L1), CD47), RORC, IFNGR1, STAT1 and JAK2 were upregulated in the ImmuneScoreH cluster, whereas FTO, CRY1, RORB, and PER1 were downregulated. Atheromatous plaques in the ImmuneScoreH cluster had higher proportions of M0 macrophages and gamma delta T cells but lower proportions of plasma cells and monocytes (p < 0.05). CAPG, CECR1, IL18, IGSF6, FBP1, HLA-DPA1 and MMP7 were commonly related to these immune cells. In addition, the advanced-stage carotid plaques in GSE28829 exhibited higher immune infiltration than early-stage carotid plaques. Conclusions Atheromatous plaques with higher immune scores were likely at a more clinically advanced stage. The progression of atherosclerosis might be related to CAPG, IGSF6, IL18, CECR1, FBP1, MMP7, FTO, CRY1, RORB, RORC, PER1, HLA-DPA1 and immune-related pathways (IFN-γ pathway and PD-1 signalling pathway). These genes and pathways might play important roles in regulating immune cells such as M0 macrophages, gamma delta T cells, plasma cells and monocytes and might serve as potential therapeutic targets for atherosclerosis.

High UBE2T mRNA expression and its prognostic significance in Ovarian cancer: a study based on data mining

2020 ◽  
Author(s):  
Fu-Cheng Cai
Keyword(s):  
Ovarian Cancer ◽  
Dendritic Cell ◽  
Prognostic Significance ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Rna Degradation ◽  
Gene Set Enrichment Analysis ◽  
Pathogenesis Related ◽  
Biologic Effect ◽  
The Difference

Abstract Background Ovarian cancer (OC) affects about 22 000 women annually in the US and ranks 5th in cancer deaths, largely due to diagnosed with advanced stage. Epithelial ovarian cancer (EOC) accounts for approximately 90% of all ovarian cancer cases. Our study was to assess the prognostic meaningful of UBE2T expression in OC dependent on data acquired from TCGA and so as to increase further knowledge into the biological pathways involved in OC pathogenesis related to UBE2T. Methods Information on gene expression and comparing clinical data were recognized and downloaded from TCGA. Gene set enrichment analysis (GSEA) created an arranged list of all genes s indicated by their connection with UBE2T expression. Results The scatter plot showed the difference of UBE2T expression between normal and tumor samples ( P <0.01). So as to decide the biological interaction network of UBE2T in OC, we used to tab Network in cBioPortal and the 50 most as often altered neighbor genes of UBE2T were demonstrated utilizing Network and the most frequent alterations were HES1. The GSEA results showed that cell cycle, DNA replication, RNA degradation, some cancers, spliceosome, Huntington’s disease, oxidative phosphorylation are differentially enriched in UBE2T high expression phenotype. Cumulative survive showed that dendritic cell of immune infiltrates statistically significant ( P <0.05) of UBE2T in OC suggesting that dendritic cell significantly affecting the prognosis, it is worth more research and exploration. Conclusion Our study found that the expression of UBE2T was significantly increased in OC patients and associated with several clinical features. UBE2T may be a potentially useful prognostic molecular biomarker of bad survival in OC, while further experimental ought to be performed to demonstrate the biologic effect of UBE2T.

scholarly journals Prognostic significance of WT1 expression in soft tissue sarcoma

2014 ◽  
Vol 12 (1) ◽  
pp. 214 ◽  
Author(s):  
Ahrong Kim ◽  
Eun Park ◽  
Kyungbin Kim ◽  
Jeong Lee ◽  
Dong Shin ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Prognostic Significance

scholarly journals Bioinformatics Approach to Identify Common Gene Signatures of Patients With Coronavirus 2019 and Lung Adenocarcinoma

2021 ◽  
Author(s):  
Xiao Liang ◽  
Yali Chen ◽  
Yuchao Fan
Keyword(s):  
Lung Adenocarcinoma ◽  
Severe Disease ◽  
Enrichment Analysis ◽  
Immune Checkpoints ◽  
Specific Gene ◽  
Ppi Network ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Protein Protein Interaction ◽  
Tf Gene

Abstract Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman’s correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), cellular component (CC) as well as to pathways, specific organs, cells and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.

The prognostic significance of surgical treatment for excessive elderly patients with soft tissue sarcoma

2018 ◽  
Vol 23 (4) ◽  
pp. 775-782 ◽  
Author(s):  
Hiroyuki Tsuchie ◽  
Makoto Emori ◽  
Hiroyuki Nagasawa ◽  
Naohisa Miyakoshi ◽  
Yasutaka Murahashi ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Elderly Patients ◽  
Prognostic Significance

scholarly journals Identification of Crucial Genes and Infiltrating Immune Cells Underlying Sepsis-Induced Cardiomyopathy via Weighted Gene Co-Expression Network Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Juexing Li ◽  
Lei Zhou ◽  
Zhenhua Li ◽  
Shangneng Yang ◽  
Liangyue Tang ◽  
...  
Keyword(s):  
Network Analysis ◽  
Immune Cells ◽  
Plasma Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Cardiac Metabolism ◽  
Gene Set Enrichment Analysis ◽  
Hub Genes ◽  
Research Studies

Sepsis-induced cardiomyopathy (SIC), with a possibly reversible cardiac dysfunction, is a potential complication of septic shock. Despite quite a few mechanisms including the inflammatory mediator, exosomes, and mitochondrial dysfunction, having been confirmed in the existing research studies we still find it obscure about the overall situation of gene co-expression that how they can affect the pathological process of SIC. Thus, we intended to find out the crucial hub genes, biological signaling pathways, and infiltration of immunocytes underlying SIC. It was weighted gene co-expression network analysis that worked as our major method on the ground of the gene expression profiles: hearts of those who died from sepsis were compared to hearts donated by non-failing humans which could not be transplanted for technical reasons (GSE79962). The top 25 percent of variant genes were abstracted to identify 10 co-expression modules. In these modules, brown and green modules showed the strongest negative and positive correlation with SIC, which were primarily enriched in the bioenergy metabolism, immunoreaction, and cell death. Next, nine genes (LRRC39, COQ10A, FSD2, PPP1R3A, TNFRSF11B, IL1RAP, DGKD, POR, and THBS1) including two downregulated and seven upregulated genes which were chosen as hub genes that meant the expressive level of which was higher than the counterparts in control groups. Then, the gene set enrichment analysis (GSEA) demonstrated a close relationship of hub genes to the cardiac metabolism and the necroptosis and apoptosis of cells in SIC. Concerning immune cells infiltration, a higher level of neutrophils and B cells native and a lower level of mast cells resting and plasma cells had been observed in patients with SIC. In general, nine candidate biomarkers were authenticated as a reliable signature for deeper exploration of basic and clinical research studies on SIC.

scholarly journals Long-Term Clinical Responses of Neoadjuvant Dendritic Cell Infusions and Radiation in Soft Tissue Sarcoma

Sarcoma ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shailaja Raj ◽  
Marilyn M. Bui ◽  
Gregory Springett ◽  
Anthony Conley ◽  
Sergio Lavilla-Alonso ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Neoadjuvant Treatment ◽  
Soft Tissue Sarcomas ◽  
External Beam Radiation ◽  
Serious Adverse Events ◽  
Clinical Safety ◽  
Beam Radiation ◽  
Clinical Responses

Purpose. Patients with large >5 cm, high-grade resectable soft tissue sarcomas (STS) have the highest risk of distant metastases. Previously we have shown that dendritic cell (DC) based vaccines show consistent immune responses.Methods. This was a Phase I single institution study of neoadjuvant radiation with DC injections on 18 newly diagnosed high-risk STS patients. Neoadjuvant treatment consisted of 50 Gy of external beam radiation (EBRT), given in 25 fractions delivered five days/week, combined with four intratumoral injections of DCs followed by complete resection. The primary endpoint was to establish the immunological response to neoadjuvant therapy and obtain data on its clinical safety and outcomes.Results. There were no unexpected toxicities or serious adverse events. Twelve out of 18 (67%) patients were alive, of which an encouraging 11/18 (61%) were alive with no systemic recurrence over a period of 2–8 years. Favorable immunological responses correlated with clinical responses in some cases.Conclusions. This study provides clinical support to using dendritic cell injections along with radiation in sarcomas, which when used optimally in combination can help clinical outcomes in soft tissue sarcoma. Study registration number isNCT00365872.

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