scholarly journals Prognostic Signature based on Transcriptome Characteristics of the C-C Motif Chemokine Receptor Genes in Hepatocellular Carcinoma and Validation

2021 ◽  
Author(s):  
Xin Zhou ◽  
Ju-sen Nong ◽  
Tian-man Li ◽  
Zhong-liu Wei ◽  
Chen-lu Lan ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Chemokine Receptor ◽  
Cell Receptor ◽  
Clinicopathological Characteristics ◽  
Signal Pathway ◽  
Prognostic Signature ◽  
Expression Levels ◽  
Chemokine Signaling ◽  
Receptor Signal ◽  
Chemokine Signaling Pathway

Abstract Object: This investigation aimed to assess the clinical significance of C-C motif chemokine receptor (CCR) genes in HCC and construct the prognostic signature based on transcriptome characteristics of the CCRs. Methods: Clinical significance of CCRs were evaluated in TCGA database and GSE14520 dataset, and prognostic CCRs (CCR1,5,7) were screened out for validation and further analysis. The relationships between CCR1,5,7 and prognosis were then evaluated in the Guangxi cohort. Based on the expression levels of CCR1,5,7 and clinicopathological characteristics, the nomograms and prognostic signatures were respectively constructed in GSE14520 dataset and Guangxi cohort. Results: CCR1,5,7 were associated with overall survival of the HCC patients in GSE14520 database, TCGA database or Guangxi cohort. In the prognostic signature, the accuracy of prognosis risk assessment based on CCR1,5,7 expression was satisfactory. The nomogram constructed in terms of the expression levels of CCR1,5,7 and clinicopathological characteristics provided a convenient tool for clinician to assess the prognostic risk of each patient. GSEA results suggested that CCRs were mainly related to B cell receptor signal pathway, chemokine signaling pathway, T cell receptor signal pathway, etc. In addition, we also found that CCR1,5,7 were significantly positively correlated with the degree of immune infiltration of B cells, T cells, and macrophagesConclusion: CCR1,5,7 might serve as prognostic biomarkers in HCC; CCR1,5,7 might regulate the progression of HCC by impacting immune cells infiltration.

scholarly journals The clinical significance of glutathione peroxidase 2 in glioblastoma multiforme

2021 ◽  
Vol 12 (1) ◽  
pp. 032-039
Author(s):  
Bangming Guo ◽  
Wenjuan Liao ◽  
Shusheng Wang
Keyword(s):  
Glioblastoma Multiforme ◽  
Glutathione Peroxidase ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Clinical Significance ◽  
Cancer Cell ◽  
Statistical Significance ◽  
Adult Brain ◽  
Chemokine Signaling ◽  
Chemokine Signaling Pathway

Abstract Background Glioblastoma multiforme (GBM) is the leading cause of death among adult brain cancer patients. Glutathione peroxidase 2 (GPX2), as a factor in oxidative stress, plays an important role in carcinogenesis. However, its role in GBM has not been well established. The study aimed to investigate the clinical significance of GPX2 with GBM prognosis. Methods Data of GBM and healthy individuals were retrospectively collected from oncomine, cancer cell line encyclopedia (CCLE), gene expression profiling interactive analysis (GEPIA), UALCAN, and Human Protein Atlas. GPX2 mRNA expression was first assessed across various cancer types in oncomine and cancer cell lines from CCLE. The mRNA expression of GPX2 was compared between normal and GBM tissues using GEPIA (normal = 207; GBM = 163) and UALCAN (normal = 5; GBM = 156). The GPX2 methylation was analyzed using data from UALCAN (normal = 2; GBM = 140). The prognostic value of GPX2 in GBM was explored in GEPIA and UALCAN using Kaplan–Meier method. STRING database was used to construct protein–protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Statistical significance was set as <0.05. Results The current study revealed no significant differences in GPX2 expression between normal and GBM from GEPIA data (P > 0.05) and UALCAN (P = 0.257). Patients with higher GPX2 intended to have a poorer prognosis (P = 0.0089). The KEGG pathways found that chemokine-signaling pathway were the more preferred. Conclusions The findings demonstrated that GPX2 might be a potential diagnosis and prognostic indicator for GBM. Chemokine-signaling pathway may be involved in GPX2 function.

scholarly journals Specific Differentially Methylated and Expressed Genes in People with Longevity Family History

2021 ◽  
Author(s):  
Chunhong LI ◽  
Qingqing NONG ◽  
Bin GUAN ◽  
Haoyu HE ◽  
Zhiyong ZHANG
Keyword(s):  
Family History ◽  
Signaling Pathway ◽  
Killer Cell ◽  
Cell Receptor ◽  
Human Longevity ◽  
Chemokine Signaling ◽  
Differentially Methylated Genes ◽  
Receptor Signaling Pathway ◽  
Chemokine Signaling Pathway ◽  
And Control

Background: We attempt to identify specific differentially methylated and expressed genes in people with longevity family history, it will contribute to discover significant features about human longevity. Methods: A prevalence study was conducted during October 2017 to January 2019 in Bama County of Guangxi, China and individuals were recruited and grouped into longevity family (n=60) and non-longevity family (n=60) to identify differentially methylated genes (DMGs). The expression profile dataset GSE16717 was downloaded from the GEO database in which individuals were divided into 3 groups, namely longevity (n=50), longevity offspring (n=50) and control (n=50) for identifying differentially expressed genes (DEGs). It was considered significantly different when P or adjusted P0.05. Results: In total, 117 longevity-related hypermethylated genes enriched in interleukin secretion/production regulation, chemokine signaling pathway and natural killer cell-mediated cytotoxicity. Another 296 significant key longevity-related DEGs primarily involved in protein binding, nucleus, cytoplasm, T cell receptor signaling pathway and Metabolic pathway, H19 and PFKFB4 were found to be both methylated and downregulated in people with longevity family history. Conclusion: Human longevity-specific genes involve in many immunity regulations and cellular immunity pathways, H19 and PFKFB4 show hypermethylated and suppressed status in people with longevity family history and might serve as longevity candidate genes.

scholarly journals Spatio-temporal regulation of concurrent developmental processes by generic signaling downstream of chemokine receptors

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Divyanshu Malhotra ◽  
Jimann Shin ◽  
Lilianna Solnica-Krezel ◽  
Erez Raz
Keyword(s):  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Specific Response ◽  
Temporal Regulation ◽  
Chemokine Signaling ◽  
Receptor Signal ◽  
Discrete Responses ◽  
Cell Type Specific ◽  
Spatio Temporal ◽  
Eukaryotic Organisms

Chemokines are secreted proteins that regulate a range of processes in eukaryotic organisms. Interestingly, different chemokine receptors control distinct biological processes, and the same receptor can direct different cellular responses, but the basis for this phenomenon is not known. To understand this property of chemokine signaling, we examined the function of the chemokine receptors Cxcr4a, Cxcr4b, Ccr7, Ccr9 in the context of diverse processes in embryonic development in zebrafish. Our results reveal that the specific response to chemokine signaling is dictated by cell-type-specific chemokine receptor signal interpretation modules (CRIM) rather than by chemokine-receptor-specific signals. Thus, a generic signal provided by different receptors leads to discrete responses that depend on the specific identity of the cell that receives the signal. We present the implications of employing generic signals in different contexts such as gastrulation, axis specification and single-cell migration.

scholarly journals A novel prognostic signature of immune-related lncRNA pairs in lung adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yang Liu ◽  
Qiuhong Wu ◽  
Xuejiao Fan ◽  
Wen Li ◽  
Xiaogang Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Risk Model ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Specific Expression ◽  
Expression Levels ◽  
Cancer Genome Atlas

AbstractLung adenocarcinoma (LUAD) is the most common subtype of lung cancer, but the prognosis of LUAD patients remains unsatisfactory. Here, we retrieved the RNA-seq data of LUAD cohort from The Cancer Genome Atlas (TCGA) database and then identified differentially expressed immune-related lncRNAs (DEirlncRNAs) between LUAD and normal controls. Based on a new method of cyclically single pairing along with a 0-or-1 matrix, we constructed a novel prognostic signature of 8 DEirlncRNA pairs in LUAD with no dependence upon specific expression levels of lncRNAs. This prognostic model exhibited significant power in distinguishing good or poor prognosis of LUAD patients and the values of the area under the curve (AUC) were all over 0.70 in 1, 3, 5 years receiver operating characteristic (ROC) curves. Moreover, the risk score of the model could serve as an independent prognostic factor for patients with LUAD. In addition, the risk model was significantly associated with clinicopathological characteristics, tumor-infiltrating immune cells, immune-related molecules and sensitivity of anti-tumor drugs. This novel signature of DEirlncRNA pairs in LUAD, which did not require specific expression levels of lncRNAs, might be used to guide the administration of patients with LUAD in clinical practice.

scholarly journals The Mutation of Ednrb(c.857 T > C) Associated With Atrophied Spleen Phenotype in Mice 

2021 ◽  
Author(s):  
Fei Wu ◽  
Mei Li ◽  
Fu-Wen Wang ◽  
Yuan Gao ◽  
Tariq Munir ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Signal Pathway ◽  
Hippo Signaling ◽  
Wild Type ◽  
Hippo Signaling Pathway ◽  
Chemokine Signaling ◽  
Chemokine Signaling Pathway ◽  
Upregulated Genes ◽  
Small Spleen

Abstract Background:The endothelin signaling pathway plays an important function in the migration, proliferation, and differentiation of neural crest cells. Endothelin receptor B (EDNRB) was reported to have a small spleen phenotype in its deficient mouse model .In our study, we also found that the mutation of EDNRB gene (c. 857 T > c) led to an atrophied spleen phenotype in mice. Different genotypes of EDNRB were significantly correlated with the spleen-kidney ratio, and the spleen phenotypes of Ednrbm1yzcm mice were smaller. The results of the tissue section and H&E staining showed that the spleen microstructure of Ednrbm1yzcm mice was abnormal. In order to explore the molecular mechanism, three groups of Ednrbm1yzcm and wild-type mice were used as control, and standard |log2(FoldChange)|>1 and Padj<0.05 were used to study the influence of EDNRB gene mutation on spleen transcriptional group in mice. GO and KEGG enrichment analysis was conducted to explore the signal pathway related to small spleen phenotype.Results: Through sequencing of mouse spleen transcriptome, 121 differentially expressed genes were selected. Results of the KEGG pathway enrichment analysis showed that in Ednrbm1yzcm mice, upregulated genes were significantly enriched in the Hippo signaling pathway, this pathway inhibits cell growth and modulates organs size and volume; and down-regulation of immune functionally associated pathways such as cytokine receptor interaction and chemokine signaling pathway. In addition, chemokine of Chemokine signaling pathway may also be related to the development of spleen immune tissue structure.Conclusions: In the experiment, we found that mice with mutations in the EDNRB gene have features such as an atrophied spleen and changes in the structure of the spleen. In order to explore the reasons, we performed RNA sequencing on three groups of Edrnrbm1yzcm and wild-type mice, and we found that upregulated genes were significantly enriched in the Hippo signaling pathway. And this signal Pathway is a proven signaling pathway that controls organ size and immune function, so we speculate that the size of the spleen may be related to the Hippo signaling pathway. This study provides a theoretical study of the mechanism of spleen development.

scholarly journals Network-Based Association Study of Obesity and Type 2 Diabetes with Gene Expression Profiles

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Siyi Zhang ◽  
Bo Wang ◽  
Jingsong Shi ◽  
Jing Li
Keyword(s):  
Type 2 Diabetes ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Receptor ◽  
Mapk Signaling ◽  
Chemokine Signaling ◽  
Chemokine Signaling Pathway

The increased prevalence of obesity and type 2 diabetes (T2D) has become an important factor affecting the health of the human. Obesity is commonly considered as a major risk factor for the development of T2D. However, the molecular mechanisms of the disease relations are not well discovered yet. In this study, the combination of multiple differential expression profiles and a comprehensive biological network of obesity and T2D allowed us to identify and compare the disease-responsive active modules and subclusters. The results demonstrated that the connection between obesity and T2D mainly relied on several pathways involved in the digestive metabolism, immunization, and signal transduction, such as adipocytokine, chemokine signaling pathway, T cell receptor signaling pathway, and MAPK signaling pathways. The relationships of almost all of these pathways with obesity and T2D have been verified by the previous reports individually. We also found that the different parts in the same pathway are activated in obesity and T2D. The association of cancer, obesity, and T2D was identified too here. As a conclusion, our network-based method not only gives better support for the close connection between obesity and T2D, but also provides a systemic view in understanding the molecular functions underneath the links. It should be helpful in the development of new therapies for obesity, T2D, and the associated diseases.

scholarly journals A Novel Prognostic Signature of Immune-related lncRNA Pairs in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Yang Liu ◽  
Qiuhong Wu ◽  
Xuejiao Fan ◽  
Wen Li ◽  
Xiaogang Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Risk Model ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Specific Expression ◽  
Expression Levels ◽  
Cancer Genome Atlas

Abstract Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, but the prognosis of LUAD patients remains unsatisfactory. Here, we retrieved the RNA-seq data of LUAD cohort from The Cancer Genome Atlas (TCGA) database and then identified differentially expressed immune-related lncRNA (DEirlncRNA) pairs between LUAD and normal controls. Based on the novel method of cyclically single pairing along with a 0-or-1 matrix, we constructed a novel prognostic signature of 8 DEirlncRNA pairs in LUAD with no dependence upon specific expression levels of lncRNAs. The prognostic model exhibited significant power in distinguishing good or poor prognosis of LUAD patients and values of the area under the curve (AUC) were all over 0.70 in 1, 3, 5 years ROC curves. Moreover, the risk model was significantly associated with clinicopathological characteristics, tumor-infiltrating immune cells, immune-related molecules and sensitivity of anti-tumor drugs. This novel signature of DEirlncRNA pairs in LUAD, which did not require specific expression levels of lncRNAs, might be used to guide the administration of patients with LUAD in clinical practice.

scholarly journals Novel Immune Subtypes Identification of HER2 Positive Breast Cancer Based On Immunogenomic Landscape

2021 ◽  
Author(s):  
Lingli Huang ◽  
Xin Liu ◽  
Li Li ◽  
Lei Wang ◽  
Nan Wu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Antigen Processing ◽  
Immune Cell ◽  
Killer Cell ◽  
Cell Receptor ◽  
Receptor Signaling ◽  
Nf Kappa B ◽  
Her2 Positive ◽  
Chemokine Signaling ◽  
Chemokine Signaling Pathway

Abstract Background: HER2 positive BC is heterogeneous. But few studies discussed the classification of HER2 positive BC based on immune-related signatures.Methods: Using two publicly BC genomics datasets, we classified HER2 positive BC based on 33 immune-related signatures and used unsupervised machine learning methods to predict and perform the classification.Results: We grouped three HER2 positive BC subtypes that we called Immune-High (IM-H), Immune-Medium (IM-M), and Immune-Low (IM-L), and manifested this categorization was predictable, duplicable and reliable by analyzing another dataset. Compared to other subtypes, IM-H had a higher immune cell infiltration level and stronger anti-tumor immune activities, as well as better clinical survival outcome. Besides these signatures, there were some cancer-related pathways which were hyperactivated in IM-H, including cytokine-cytokine receptor interactions, antigen processing and presentation pathways, natural killer cell-mediated cytotoxicity, Th1 and Th2 cell differentiation, chemokine signaling pathway, Th17 cell differentiation, B and T cell receptor signaling, NF-kappa B signaling, PD-L1 expression and PD-1 checkpoint pathway in cancer, TNF signaling, IL-17 signaling, NOD-like receptor signaling and Toll-like receptor signaling. By contrast, IM-L showed depressed immune-related signatures and enhanced activation of lycosylphosphatidylinositol-anchor biosynthesis and mismatch repair. Moreover, we discovered a gene co-expression network focused on eight transcription factor genes (EOMES, TBX21, GFI1, IRF4, POU2AF1, CIITA, FOXP3 and TOX) and one tumor suppress gene (PRF1), which were closely related with tumor immune.Conclusion: We identified three HER2 positive BC subtypes based on immune-related signatures, which had potential clinical implications and promoted the optimal stratification of HER2 positive BC responsive to immunotherapy.

scholarly journals Role of JAK-STAT Pathway in Broiler Chicks Fed with Chestnut Tannins

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 337
Author(s):  
Annah Lee ◽  
Gabriela Cardoso Dal Pont ◽  
Michele Battaglia ◽  
Ryan J. Arsenault ◽  
Michael H. Kogut
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Immune Modulation ◽  
Cell Receptor ◽  
Host Immunity ◽  
Broiler Chicks ◽  
Chemokine Signaling ◽  
Chemokine Signaling Pathway ◽  
Stat Pathway

The objective of this study was to identify the phosphorylation events associated with host immunity with the inclusion of chestnut tannins (ChT) in the diet. A total of 200 male day-of-hatch Cobb 500 chicks were randomly assigned to two treatment groups, totaling 50 chicks per pen per experiment (this study was repeated two times). The treatments were as follows: (1) control feed—normal starter feed (n = 50), and (2) 1% ChT inclusion feed (n = 50). The ceca were collected on each necropsy day for analysis via (1) a peptide array to provide tissue immunometabolism information from the host, and (2) quantitative PCR for mRNA expression. Of the top three immune pathways, the data identified the T-cell receptor signaling pathway, the chemokine signaling pathway, and the JAK-STAT signaling pathway. The results showed significantly altered phosphorylation of JAK and STAT peptides within the JAK-STAT pathway. These results support the mRNA expression data with the upregulated IL-6 response, due to the significant phosphorylation of IL6ST, JAK, and STAT peptides. In regard to immune modulation, ChT appear to influence host immunity via an IL-6 mediated response which could be beneficial in host defenses against pathogens at the early stages of broiler growth and development. Therefore, it is suggested that the role of the JAK-STAT pathway is altered by including ChT in the diet.

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