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 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 Pan-Cancer Analysis of PIMREG as a Biomarker for the Prognostic and Immunological Role

2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Zhu ◽  
Xinyao Hu ◽  
Yingze Ye ◽  
Zhihong Jian ◽  
Yi Zhong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Chemokine Receptors ◽  
Antigen Processing ◽  
Immune Cell ◽  
Nk Cell ◽  
Cell Lineage ◽  
Cell Receptor ◽  
The Cancer Genome Atlas ◽  
Cancer Types ◽  
Pan Cancer

Phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) localizes to the nucleus and can significantly elevate the nuclear localization of clathrin assembly lymphomedullary leukocythemia gene. Although there is some evidence to support an important action for PIMREG in the occurrence and development of certain cancers, currently no pan-cancer analysis of PIMREG is available. Therefore, we intended to estimate the prognostic predictive value of PIMREG and to explore its potential immune function in 33 cancer types. By using a series of bioinformatics approaches, we extracted and analyzed datasets from Oncomine, The Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia (CCLE) and the Human Protein Atlas (HPA), to explore the underlying carcinogenesis of PIMREG, including relevance of PIMREG to prognosis, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME) and infiltration of immune cells in various types of cancer. Our findings indicate that PIMREG is highly expressed in at least 24 types of cancer, and is negatively correlated with prognosis in major cancer types. In addition, PIMREG expression was correlated with TMB in 24 cancers and with MSI in 10 cancers. We revealed that PIMREG is co-expressed with genes encoding major histocompatibility complex, immune activation, immune suppression, chemokine and chemokine receptors. We also found that the different roles of PIMREG in the infiltration of different immune cell types in different tumors. PIMREG can potentially influence the etiology or pathogenesis of cancer by acting on immune-related pathways, chemokine signaling pathway, regulation of autophagy, RIG-I like receptor signaling pathway, antigen processing and presentation, FC epsilon RI pathway, complement and coagulation cascades, T cell receptor pathway, NK cell mediated cytotoxicity and other immune-related pathways. Our study suggests that PIMREG can be applied as a prognostic marker in a variety of malignancies because of its role in tumorigenesis and immune infiltration.

scholarly journals Identification of Key mRNAs and lncRNAs in Neonatal Sepsis by Gene Expression Profiling

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Lin Bu ◽  
Zi-wen Wang ◽  
Shu-qun Hu ◽  
Wen-jing Zhao ◽  
Xiao-juan Geng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neonatal Sepsis ◽  
Ribosome Biogenesis ◽  
Cell Lineage ◽  
Cell Receptor ◽  
Rna Degradation ◽  
Receptor Signaling ◽  
Nf Kappa B ◽  
Ppi Networks ◽  
Receptor Signaling Pathway

Neonatal sepsis is one of the most prevalent causes of death of the neonates. However, the mechanisms underlying neonatal sepsis remained unclear. The present study identified a total of 1128 upregulated mRNAs and 1008 downregulated mRNAs, 28 upregulated lncRNAs, and 61 downregulated lncRNAs in neonatal sepsis. Then, we constructed PPI networks to identify key regulators in neonatal sepsis, including ITGAM, ITGAX, TLR4, ITGB2, SRC, ELANE, RPLP0, RPS28, RPL26, and RPL27. lncRNA coexpression analysis showed HS.294603, LOC391811, C12ORF47, LOC729021, HS.546375, HNRPA1L-2, LOC158345, and HS.495041 played important roles in the progression of neonatal sepsis. Bioinformatics analysis showed DEGs were involved in the regulation cellular extravasation, acute inflammatory response, macrophage activation of NF-kappa B signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, Toll-like receptor signaling pathway, and ribosome, RNA transport, and spliceosome. lncRNAs were involved in regulating ribosome, T cell receptor signaling pathway, RNA degradation, insulin resistance, ribosome biogenesis in eukaryotes, and hematopoietic cell lineage. We thought this study provided useful information for identifying novel therapeutic markers for neonatal sepsis.

scholarly journals The Bitter the Taste, The Better is the Medicine: Is Caffeine the Answer to COVID-19?

2020 ◽  
Author(s):  
Devyani Sharma ◽  
Ashutosh Bansal
Keyword(s):  
Signaling Pathways ◽  
Host Defense ◽  
Respiratory System ◽  
Defense Mechanisms ◽  
Killer Cell ◽  
Taste Receptor ◽  
Cell Receptor ◽  
Respiratory Dysfunction ◽  
Chemokine Signaling ◽  
T Cell Receptor Signaling

Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. The virus is mainly transmitted through droplets generated when an infected person coughs, sneezes, or exhales. The firsthand reason for COVID 19 is upper respiratory dysfunction which allows the entry of viruses in the respiratory system and leads to severe problems in the human body. Thus, Bitter taste receptor, TAS2Rs on human airway smooth muscle (ASM) found in the respiratory system can play a big role in providing immunity against COVID-19. Activation of TAS2Rs by bitter agonists activates host defense pathways through calcium signaling. Cytokines storms is the another reason for COVID -19 that can be prevented by TAS2Rs because it can regulate natural killer cell-mediated cytotoxicity, chemokine signaling pathways, T cell receptor signaling pathways, TNF signaling pathways, and others. Since, we propose to utilize caffeine, the bitter agonists to stimulate the TAS2Rs, activating host defense mechanisms and also suppressing the cytokine storms due to its anti-inflammatory action, altogether leading to an ameliorated effects of COVID-19.

scholarly journals Prognostic Biomarkers and Therapeutic Targets Identification Among CXC Chemokines in the Colon Adenocarcinoma Microenvironment

2022 ◽  
Author(s):  
Heng Wang ◽  
ChangQing Guo ◽  
Jun Luo ◽  
Quan Li ◽  
BuQing Fu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Cell Activity ◽  
Colon Adenocarcinoma ◽  
Prognostic Indicators ◽  
Chemokine Signaling ◽  
High Incidence ◽  
High Incidence Rate ◽  
Chemokine Signaling Pathway

Abstract Background: COAD is among the most prevalent malignancy, with a very high incidence rate. Crosstalk between cancer and interstitial cells significantly affects cancer development, modulated partly by chemokines production. When present in the tumor microenvironment, CXC chemokines have been shown to regulate tumor cell activity and influence immune cell transport, resulting in anti-tumor immune mechanisms and influencing the outcomes of the patient; nonetheless, the CXC chemokines expression levels in COAD, as well as their prognostic significance, have not yet been established.Methods: This study used UALCAN, GeneMANIA, STRING, TRRUST, cBioPortal, TIMER, and GEPIA,Results: The expression of CXC1/2/3/5/6/11/12/13/14/16/17 in COAD patients was shown to be significantly correlated with the pathological stage. A considerably improved prognosis was observed in patients with low transcriptional levels of CXCL9/10/11. Differentially expressed CXC chemokines exert roles that are predominantly correlated with the chemokine signaling pathway and interactions of cytokine–cytokine receptors. Our findings indicated that the transcriptional factors, including SP1, RELA, and NFKB1 are essential for the production of CXC chemokines. Furthermore, we discovered a substantial association between the CXC chemokines production and infiltration of 6 kinds of immune cells (CD8+ T cells, dendritic cells, B cells, CD4+ T cells, neutrophils, and macrophages,). Conclusions: These findings might be useful in identifying prognostic indicators and immunotherapeutic targets for colon cancer.

scholarly journals Identification of Tumor Microenvironment-related Prognostic Genes in Colorectal Cancer based on Bioinformatic Methods

2021 ◽  
Author(s):  
Yi Liu ◽  
Long Cheng ◽  
Chao Li ◽  
Chen Zhang ◽  
Wang Lei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Functional Enrichment ◽  
Receptor Interaction ◽  
Ppi Networks ◽  
Chemokine Signaling ◽  
Chemokine Signaling Pathway

Abstract Colorectal cancer (CRC) ranks fourth among the deadliest cancers globally, and the progression is highly affected by the tumor microenvironment (TME). This study explores the relationship between TME and colorectal cancer prognosis and identifies prognostic genes related to the CRC microenvironment. We collected the gene expression data from The Cancer Genome Atlas (TCGA) and calculated the scores of stromal/immune cells and their relations to clinical outcomes in colorectal cancer by the ESTIMATE algorithm. Lower immune scores were significantly related to malignant progression of CRC (stage, p=0.014; metastasis, p=0.001). We screened 292 differentially expressed genes (DEGs) by dividing CRC cases into high and low stromal/immune score groups. Functional enrichment analyses and protein-protein interaction (PPI) networks illustrated that these DEGs were closely involved in immune response, cytokine-cytokine receptor interaction, and chemokine signaling pathway. Six DEGs (FABP4, MEOX2, MMP12, ERMN, TNFAIP6, and CHST11) with prognostic value were identified by survival analysis and validated in an independent cohort (GSE17386). The six DEGs were significantly related to immune cell infiltration levels based on the Tumor Immune Estimation Resource (TIMER). The results might contribute to discovering new diagnostic and prognostic biomarkers and new treatment targets for colorectal cancer.

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.

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