scholarly journals Short Survival-Related Genes Harbor EMT Processes and Dendritic Cell Infiltration in Glioblastoma

2020 ◽  
Author(s):  
Zhenkun Yang ◽  
Bo Zhang ◽  
Zhenhao Zhang ◽  
Jingjing Wang ◽  
Yaling Hu ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Infiltration ◽  
Biological Processes ◽  
Ppi Network ◽  
Hub Genes ◽  
Short Term ◽  
Upregulated Genes ◽  
Long Term Survivors ◽  
Sr Genes

Abstract Background: Glioblastoma is an aggressive primary tumour with the lowest survival time among brain tumours. Tumour-infiltrating immune cells (TIICs) are involved in tumour progression and determine the prognosis, while the association of immune cell infiltration with glioblastoma is rarely unknown. This study aimed to screen survival-related (SR) genes and major biological processes through bioinformatic analysis and to identify the relationship between SR genes and TIICs.Methods:SR genes were screened by comparing the long-term (>36 months) and short-term (<12 months) survivors in the database GSE53733. Gene set enrichment analysis (GSEA) was applied to compare the differences in biological processes between long-term survivors and short-term survivors. The SR genes were identified using the limma package of R. Gene Ontology (GO) analysis was conducted through Metascape. The protein-protein interaction (PPI) network of the SR genes was established through the Search Tool for the Retrieval of Interacting Genes (STRING) website and further analysed by the Molecular Complex Detection (MCODE) algorithm. UALCAN and GlioVis were employed to analyse the expression levels and prognostic value of hub genes. The correlation of hub genes with immune cell filtration was estimated by the Tumor Immune Estimation Resource (TIMER). The gene-drug interaction network was constructed using the Comparative Toxicogenomics Database (CTD).Results: The functions of the detected genes were mainly enriched in epithelial mesenchymal transition (EMT) and oxidative phosphorylation. Of the detected genes, a total of 220 SR genes were identified, including 78 upregulated genes and 142 downregulated genes in long-term survivors. The upregulated genes were mainly related to neuron projection morphogenesis, extracellular matrix, and cation channel activity. The downregulated genes were mainly related to extracellular matrix organization and angiogenesis. The PPI network for SR genes was constructed with 65 edges and 195 nodes, and two significant modules were selected. The results indicated that COL1A2, COL6A2, COL8A1, and COL8A2 were hub SR genes. In addition, they were correlated with immune cell infiltration, especially dendritic cell infiltration.Conclusions: These results revealed that collagens accounted for the progression and prognosis of glioblastoma. In addition, DC infiltration is a risk factor for glioblastoma patients. The expression of collagen protein COL6A2 was significantly correlated with the DC infiltration level and poor prognosis. Further, potential drugs that affect the function of COL6A2 could improve the outcomes of glioblastoma.

scholarly journals Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes

2021 ◽  
Author(s):  
shenglan li ◽  
Zhuang Kang ◽  
jinyi Chen ◽  
Can Wang ◽  
Zehao Cai ◽  
...  
Keyword(s):  
Immune Cell ◽  
Intracranial Tumor ◽  
Cell Infiltration ◽  
Molecular Profile ◽  
Immune Cell Infiltration ◽  
Ppi Network ◽  
Hub Genes ◽  
Data Set ◽  
Hub Gene ◽  
External Data

Abstract Background Medulloblastoma is a common intracranial tumor among children. In recent years, research on cancer genome has established four distinct subtypes of medulloblastoma: WNT, SHH, Group3, and Group4. Each subtype has its own transcriptional profile, methylation changes, and different clinical outcomes. Treatment and prognosis also vary depending on the subtype. Methods Based on the methylation data of medulloblastoma samples, methylCIBERSORT was used to evaluate the level of immune cell infiltration in medulloblastoma samples and identified 10 kinds of immune cells with different subtypes. Combined with the immune database, 293 Imm-DEGs were screened. Imm-DEGs were used to construct the co-expression network, and the key modules related to the level of differential immune cell infiltration were identified. Three immune hub genes (GAB1, ABL1, CXCR4) were identified according to the gene connectivity and the correlation with phenotype in the key modules, as well as the PPI network involved in the genes in the modules. Results The subtype marker was recognized according to the immune hub, and the subtype marker was verified in the external data set, the methylation level of immune hub gene among different subtypes was compared and analyzed, at the same time, tissue microarray was used for immunohistochemical verification, and a multi-factor regulatory network of hub gene was constructed. Conclusions Identifying subtype marker is helpful to accurately identify the subtypes of medulloblastoma patients, and can accurately evaluate the treatment and prognosis, so as to improve the overall survival of patients.

scholarly journals Increased Immune Gene Expression and Immune Cell Infiltration in High-Grade Astrocytoma Distinguish Long-Term from Short-Term Survivors

2012 ◽  
Vol 189 (4) ◽  
pp. 1920-1927 ◽  
Author(s):  
Andrew M. Donson ◽  
Diane K. Birks ◽  
Stephanie A. Schittone ◽  
Bette K. Kleinschmidt-DeMasters ◽  
Derrick Y. Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Gene ◽  
Immune Cell Infiltration ◽  
High Grade ◽  
Short Term ◽  
Immune Gene Expression ◽  
High Grade Astrocytoma

scholarly journals Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes

2021 ◽  
Author(s):  
Shenglan Li ◽  
Zhuang Kang ◽  
Jinyi Chen ◽  
Can Wang ◽  
Zehao Cai ◽  
...  
Keyword(s):  
Immune Cell ◽  
Intracranial Tumor ◽  
Cell Infiltration ◽  
Molecular Profile ◽  
Immune Cell Infiltration ◽  
Ppi Network ◽  
Hub Genes ◽  
Data Set ◽  
Hub Gene ◽  
External Data

Abstract Medulloblastoma is a common intracranial tumor among children. In recent years, research on cancer genome has established four distinct subtypes of medulloblastoma: WNT, SHH, Group3, and Group4. Each subtype has its own transcriptional profile, methylation changes, and different clinical outcomes. Treatment and prognosis also vary depending on the subtype. Based on the methylation data of medulloblastoma samples, methylCIBERSORT was used to evaluate the level of immune cell infiltration in medulloblastoma samples and identified 10 kinds of immune cells with different subtypes. Combined with the immune database, 293 Imm-DEGs were screened. Imm-DEGs were used to construct the co-expression network, and the key modules related to the level of differential immune cell infiltration were identified. Three immune hub genes (GAB1, ABL1, CXCR4) were identified according to the gene connectivity and the correlation with phenotype in the key modules, as well as the PPI network involved in the genes in the modules. The subtype marker was recognized according to the immune hub, and the subtype marker was verified in the external data set, Finally, the methylation level of immune hub gene among different subtypes was compared and analyzed, at the same time, tissue microarray was used for immunohistochemical verification, and a multi-factor regulatory network of hub gene was constructed. Identifying subtype marker is helpful to accurately identify the subtypes of medulloblastoma patients, and can accurately evaluate the treatment and prognosis, so as to improve the overall survival of patients.

Identification of WDFY3 Neoantigens as Prognostic Markers in Longterm Survivors of Extrahepatic Cholangiocarcinoma

2020 ◽  
Vol 20 (11) ◽  
pp. 875-886
Author(s):  
Yingyi Wang ◽  
Bao Jin ◽  
Na Zhou ◽  
Zhao Sun ◽  
Jiayi Li ◽  
...  
Keyword(s):  
Antitumor Immunity ◽  
Prognostic Markers ◽  
Immune Cell ◽  
Neutrophil Infiltration ◽  
Computational Biophysics ◽  
Extrahepatic Cholangiocarcinoma ◽  
Whole Exome ◽  
Mutation Burden ◽  
Long Term Survivors

Background:: Neoantigens are newly formed antigens that have not been previously recognized by the immune system. They may arise from altered tumor proteins that form as a result of mutations. Although neoantigens have recently been linked to antitumor immunity in long-term survivors of cancers, such as melanoma and colorectal cancer, their prognostic and immune-modulatory role in many cancer types remains undefined. Objective: The purpose of this study is to identify prognostic markers for long-term extrahepatic cholangiocarcinoma (EHCC) survival. Methods: We investigated neoantigens in EHCC, a rare, aggressive cancer with a 5-year overall survival rate lower than 10%, using a combination of whole-exome sequencing (WES), RNA sequencing (RNA-seq), computational biophysics, and immunohistochemistry. Results: : Our analysis revealed a decreased neutrophil infiltration-related trend of high-quality neoantigen load with IC50 <500 nM (r=-0.445, P=0.043). Among 24 EHCC patients examined, we identified four long-term survivors with WDFY3 neoantigens and none with WDFY3 neoantigens in the short-term survivors. The WDFY3 neoantigens are associated with a lower infiltration of neutrophils (p=0.013), lower expression of CCL5 (p=0.025), CXCL9 (p=0.036) and TIGIT (p=0.016), and less favorable prognosis (p=0.030). In contrast, the prognosis was not significantly associated with tumor mutation burden, neoantigen load, or immune cell infiltration. Conclusion:: We suggest that the WDFY3 neoantigens may affect prognosis by regulating antitumor immunity and that the WDFY3 neoantigens may be harnessed as potential targets for immunotherapy of EHCC.

The Screening and Identification of Key Biomarkers in Adrenocortical Carcinoma: Evidence from a Bioinformatics Analysis

2022 ◽  
Vol 12 (3) ◽  
pp. 523-532
Author(s):  
Xin Yan ◽  
Chunfeng Liang ◽  
Xinghuan Liang ◽  
Li Li ◽  
Zhenxing Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Ontology ◽  
Protein Interaction ◽  
Adrenocortical Carcinoma ◽  
Gene Expression Omnibus ◽  
Heparin Binding ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Upregulated Genes

<sec> <title>Objective:</title> This study aimed to identify the potential key genes associated with the progression and prognosis of adrenocortical carcinoma (ACC). </sec> <sec> <title>Methods:</title> Differentially expressed genes (DEGs) in ACC cells and normal adrenocortical cells were assessed by microarray from the Gene Expression Omnibus database. The biological functions of the classified DEGs were examined by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses and a protein–protein interaction (PPI) network was mapped using Cytoscape software. MCODE software was also used for the module analysis and then 4 algorithms of cytohubba software were used to screen hub genes. The overall survival (OS) examination of the hub genes was then performed by the ualcan online tool. </sec> <sec> <title>Results:</title> Two GSEs (GSE12368, GSE33371) were downloaded from GEO including 18 and 43 cases, respectively. One hundred and sixty-nine DEGs were identified, including 57 upregulated genes and 112 downregulated genes. The Gene Ontology (GO) analyses showed that the upregulated genes were significantly enriched in the mitotic cytokines is, nucleus and ATP binding, while the downregulated genes were involved in the positive regulation of cardiac muscle contraction, extracellular space, and heparin-binding (P < 0.05). The Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway examination showed significant pathways including the cell cycle and the complement and coagulation cascades. The protein– protein interaction (PPI) network consisted of 162 nodes and 847 edges, including mitotic nuclear division, cytoplasmic, protein kinase binding, and cell cycle. All 4 identified hub genes (FOXM1, UBE2C, KIF11, and NDC80) were associated with the prognosis of adrenocortical carcinoma (ACC) by survival analysis. </sec> <sec> <title>Conclusions:</title> The present study offered insights into the molecular mechanism of adrenocortical carcinoma (ACC) that may be beneficial in further analyses. </sec>

Identification of Potential Genes Associated with Vemurafenib Efficacy and Melanoma Prognosis

2021 ◽  
Vol 24 ◽  
Author(s):  
Yue Qi ◽  
GuiE Ma
Keyword(s):  
Signaling Pathway ◽  
Estrogen Signaling ◽  
Akt Signaling Pathway ◽  
Ppi Network ◽  
Hub Genes ◽  
Ampk Signaling ◽  
Melanoma Patients ◽  
Key Genes ◽  
Neurotrophin Signaling ◽  
Upregulated Genes

Objective: This work aimed to investigate the molecular mechanisms underlying the efficacy of vemurafenib as a treatment for melanoma. Methods: The GSE52882 dataset, which includes A375 and A2058 melanoma cell lines treated with vemurafenib and dimethyl sulfoxide (DMSO), and clinical information associated with melanoma patients, were acquired from the Gene Expression Omnibus (GEO) database and University of California Santa Cruz (UCSC), respectively. Functional enrichment analysis, protein-protein interaction (PPI) network construction, sub-module analysis, and transcriptional regulation analysis were performed on overlapping differentially expressed genes (DEGs) identified in both cell lines. Finally, we performed a survival analysis based on the genes identified. Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients. Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients. Conclusion: MMP2, CXCL8, PIK3R3, ITGB3, and LEF1 may play roles in the efficacy of vemurafenib treatment in melanoma; for example, MMP2 and PIK3R3 are likely associated with vemurafenib resistance. These findings will contribute to the development of novel therapies for melanoma.

scholarly journals Association Between Tumor Mutation Burden and Prognosis in Lower-Grade Glioma: An Exploratory Study 

2021 ◽  
Author(s):  
Di Cao ◽  
Jun Wang ◽  
Yan Lin ◽  
Guangwei Li
Keyword(s):  
Immune Cell ◽  
Differential Expression Analysis ◽  
Cell Infiltration ◽  
Lower Grade ◽  
Immune Cell Infiltration ◽  
Hub Genes ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Lower Grade Glioma ◽  
Genome Atlas

Abstract Background: The therapeutic efficacy of immune checkpoint inhibitor therapy is highly influenced by tumor mutation burden (TMB). The relationship between TMB and prognosis in lower-grade glioma is still unclear. We aimed to explore the relationships and mechanisms between them in lower-grade glioma.Methods: We leveraged somatic mutation data from The Cancer Genome Atlas (TCGA). Clinical cases were divided into high- and low-TMB groups based on the median of TMB. Infiltrating immune cells were analyzed using CIBERSORT and differential expression analysis between the prognostic groups performed. The key genes were identified as intersecting between immune-related genes. Cox regression and survival analysis were performed on the intersecting genes. A total of 7 hub genes were identified. The effect of somatic copy number alterations (SCNA) of the hub genes on immune cell infiltration was analyzed using TIMER, which was used to determine the risk factors and immune infiltration status in LGG. Subsequently, based on hub genes, a TMB Prognosis Index (TMBPI) model was constructed to predict the risk in LGG patients. Besides, this model was validated using data from TCGA and Chinese Glioma Genome Atlas (CGGA).Results: High-TMB favored worse prognosis (P＜0.001) and macrophage infiltration was an independent risk factor (P＜0.001). In the high-TMB group (P=0.033, P=0.009), the proportion of macrophages M0 and M2 increased and monocytes decreased (P=0.006). Besides, the SCNA of the hub genes affected the level of immune cell infiltration by varying degrees among which IGF2BP3, NPNT, and PLA2G2A had a significant impact. The AUC of the ROC curve at 1-, 3- and 5-years were all above 0.74.Conclusions: This study implies that high-TMB correlated with unfavorable prognosis in lower-grade glioma. And high-TMB may have an impact on prognosis by changing tumor microenvironment, caused by the SCNAs of genes. The TMBPI model accurately predicted prognosis in LGG patients.

scholarly journals Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammed M. Almutairi ◽  
Farzane Sivandzade ◽  
Thamer H. Albekairi ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Cell Infiltration ◽  
Cellular Mechanisms ◽  
Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

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