Immune Cells Signaling-Pathway and Genomic Profiles for Personalized Immunotherapy

Abstract Background: Approximately 15–30% of patients with breast cancer (BRCA) eventually develop brain metastases (BMs) with high morbidity and mortality. Herein, we aimed to identify genes specific to breast cancer brain metastases (BCBM) from an immune infiltration perspective.Methods: GSE100534 and GSE125989 were obtained from the NCBI Gene Expression Omnibus (GEO), then performed normalization using Rstudio and perl 5. We constructed a Weighted Gene Co-Expression Network Analysis (WGCNA) and obtained differentially expressed genes (DEGs) in BMs sample compared with primary BRCA tissue. Then we performed GO and KEGG pathway analysis. The LinkedOmics and UALCAN analysis showed the expression of gene in BRCA. The Kaplan-Meier plotter database was used to evaluate the prognosis. The composition of significant tumor-infiltrating immune cells was assessed using the CIBERSORT algorithm. Spearman’s correlation analysis revealed the correlation between CILP gene and immune cells in TCGA cohort and Timer database. Using GSEA analysis, we conducted to identify the potential pathways in BCBM.Results: The cartilage intermediate layer protein (CILP) was a late event in BRCA (stage III to IV) with poor prognosis (P< 0.05). LinkedOmics showed that the mRNA expression of CILP was down-regulated in advanced cancer (P< 0.05). Besides, UALCAN analysis showed that CILP expression was downregulated in HER2-positive and triple-negative breast cancer which were more prone to BMs (P< 0.05). CILP was the hub gene which was significantly associated with BCBM identified by WGCNA (R2=−0.6, P=3e-06). We found that the resting infiltration of mast cells in the BCBM group was significantly lower than that in the primary BRCA group (P= 0.01). In addition, Spearman’s correlation analysis revealed that the expression of CILP positively correlated with that of mast cells (P< 0.05). Finally, the FCERI-mediated MAPK activation (NES=2.1847, P=0, FDR=0.0031), which could regulate mast cell activity, were enriched in BCBM.Conclusions: CILP can influence the progression of BRCA favored for BMs through meditating mast cells via the MAPK signaling pathway.

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GJA1 Expression and Its Prognostic Value in Cervical Cancer

BioMed Research International ◽

10.1155/2020/8827920 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Silu Meng ◽

Xinran Fan ◽

Jianwei Zhang ◽

Ran An ◽

Shuang Li

Keyword(s):

Gene Expression ◽

Cervical Cancer ◽

Logistic Regression ◽

Gap Junction ◽

Signaling Pathway ◽

Immune Cells ◽

Immune Cell ◽

Normal Tissues ◽

Kaplan Meier ◽

Chi Squared

Gap Junction Protein Alpha 1 (GJA1) belongs to the gap junction family and has been widely studied in cancers. We evaluated the role of GJA1 in cervical cancer (CC) using public data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. The difference of GJA1 expression level between CC and normal tissues was analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA), six GEO datasets, and the Human Protein Atlas (HPA). The relationship between clinicopathological features and GJA1 expression was analyzed by the chi-squared test and the logistic regression. Kaplan–Meier survival analysis and Cox proportional hazard regression analysis were used to assessing the effect of GJA1 expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways regulated by GJA1. Immune Cell Abundance Identifier (ImmuCellAI) was chosen to analyze the immune cells affected by GJA1. The expression of GJA1 in CC was significantly lower than that in normal tissues based on the GEPIA, GEO datasets, and HPA. Both the chi-squared test and the logistic regression showed that high-GJA1 expression was significantly correlated with keratinization, hormone use, tumor size, and FIGO stage. The Kaplan–Meier curves suggested that high-GJA1 expression could indicate poor prognosis ( p = 0.0058 ). Multivariate analysis showed that high-GJA1 expression was an independent predictor of poor overall survival (HR, 4.084; 95% CI, 1.354-12.320; p = 0.013 ). GSEA showed many cancer-related pathways, such as the p53 signaling pathway and the Wnt signaling pathway, were enriched in the high-GJA1-expression group. Immune cell abundance analysis revealed that the abundance of CD8 naive, DC, and neutrophil was significantly increased in the high-GJA1-expression group. In conclusion, GJA1 can be regarded as a potential prognostic marker of poor survival and therapeutic target in CC. Moreover, many cancer-related pathways may be the critical pathways regulated by GJA1. Furthermore, GJA1 can affect the abundance of immune cells.

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The prognostic value of a tumor microenvironment-based immune cell infiltration score model in colon cancer

10.21203/rs.3.rs-496500/v1 ◽

2021 ◽

Author(s):

Xiaofen Pan ◽

Xingkui Tang ◽

Minling Liu ◽

Xijun Luo ◽

Mengyuan Zhu ◽

...

Keyword(s):

Colon Cancer ◽

Signaling Pathway ◽

Immune Cells ◽

Evaluation System ◽

Prognostic Value ◽

Immune Cell ◽

Wnt Signaling Pathway ◽

Mapk Signaling ◽

Cell Infiltration ◽

Immune Cell Infiltration

Abstract BackgroundTumor microenvironment consists of tumor cells, immune cells and other matric components. Tumor infiltration immune cells are associated with prognosis. But all the current prognosis evaluation system dose not take tumor immune cells other matrix component into consideration. In the current study, we aimed to construct a prognosis predictive model based on tumor microenvironment.MethodCIBERSORT and ESTIMATE algorithms were used to reveal the immune cell infiltration landscape of colon cancer. Patients were classified into three clusters by ConsensusClusterPlus algorithm. Immune cell infiltration (ICI) scores of each patient were determine by principal-component analysis. Patients were divided to high and low ICI score groups. Survival, gene expression and somatic mutation of the two groups were compared.ResultsPatients with no lymph node invasion, no metastasis, T1-2 disease and stage I-II had higher ICI scores. Calcium signaling pathway, leukocyte transendothelial migration pathway, MAPK signaling pathway, TGF β pathway, and WNT signaling pathway were enriched in high ICI score group. Immune-checkpoint genes and immune-activity associated genes were significantly decreased in high ICI score. Patients in high ICI score group had better survival than low ICI score group. Prognostic value of ICI score was independent of TMB.ConclusionICI score might serve as an independent prognostic biomarker in colon cancer.

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Identification the prognostic value of immune gene signature and infiltrating immune cells of esophageal cancer patients

10.21203/rs.3.rs-20941/v1 ◽

2020 ◽

Author(s):

Lin Wang ◽

Qian Wei ◽

Ming Zhang ◽

Lianze Chen ◽

Zinan Li ◽

...

Keyword(s):

T Cells ◽

Esophageal Cancer ◽

Signaling Pathway ◽

Immune Cells ◽

Roc Curves ◽

Survival Outcome ◽

Immune Gene ◽

Prognostic Signature ◽

Immune Genes ◽

Validation Set

Abstract Background Esophageal cancer (ESCA) is one of the deadliest solid malignancies with worse survival in the world. The poor prognosis of ESCA is not only related to malignant cells, but also affected by the microenvironment. We aimed to establish prognostic signature consisting of immune genes to predict the survival outcome of patients and estimate the prognosis value of infiltrating immune cells in tumor microenvironment (TME). Methods Based on integrated analysis of gene expression profiling and immune gene database, differentially immune-related genes were filtered out. Then, stepwise Cox regression analysis was applied to identify survival related immune genes and construct prognosis signature. Functional enrichment analysis was performed to explore biology function. Kaplan-Meier (K-M) curves and receiver operating characteristic (ROC) curves were performed to validate the predictive effect of predictive signature. We also verified the clinical value of prognostic signature under the influence of different clinical parameters. For deeper analysis, we evaluated the correlation between prognosis signature and infiltrating immune cells by Tumor Immune Estimation Resource (TIMER) and CIBERSORT. Results Finally, we identified 303 differentially immune genes as candidate and constructed immune prognosis signature composed of six immune genes. Furthermore, we observed that the prognosis signature was enriched in cytokine-mediated signaling pathway, lymphocyte activation, immune effector process, cancer pathway, NF-kappa B signaling pathway. K-M survival curves showed that the prognosis signature indeed have good predictive ability in entire ESCA set ( P =0.003), validation set 1 ( P =0.008) and validation set 2 ( P =0.036). The area under the curve (AUC) of ROC curves validated the predictive accuracy of immune signature in three cohorts (AUC=0.757, 0.800 and 0.701), respectively. In addition, we identified the prognosis value of infiltrating-immune cells including activated memory CD4 T cells, T cells follicular helper cells and monocytes and provided a landscape of TME. Conclusions The results indicated that immune prognosis signature can be a novel biomarker to predict survival outcome, which can provide new targets for immunotherapy and individualized therapies in ESCA and open up a new prospect for improving the prognosis of ESCA patients in the era of immunotherapy.

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Identification of Prognostic Biomarkers and Immunotherapeutic Targets with CXC Chemokines in Glioblastoma Multiforme Using Integrated Bioinformatic Analysis

10.21203/rs.3.rs-35731/v1 ◽

2020 ◽

Author(s):

Hailing Liu ◽

Jinguang Zhu ◽

Guangwen Wang

Keyword(s):

Transcription Factors ◽

Glioblastoma Multiforme ◽

Signaling Pathway ◽

Immune Cells ◽

Disease Free Survival ◽

Bioinformatic Analysis ◽

Differentially Expressed ◽

Prognostic Biomarkers ◽

Receptor Interaction ◽

Dismal Prognosis

Abstract Background Glioblastoma multiforme (GBM) is the most malignant central nervous system tumour bearing a dismal prognosis. The study aimed to explore the potential biomarkers and therapeutic targets with CXC chemokines in GBM by integrated bioinformatics analysis.Methods Differentially expressed CXC Chemokines were identified in GBM using GEPIA and UALCAN databases,and Kaplan–Meier analyses were performed by GEPIA subsequently. Protein -protein interaction (PPI) network was established in STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were utilized to analyze differentially expressed CXC Chemokines and their similar genes gained from GEPIA. Then, we conducted transcription factors, kinase targets, and immune cells infiltration using TRRUST, LinkedOmics, and TIMER, respectively.Results The mRNA expression levels of CXCL3/5/6/9/10/11/12/13/16 in GMB were significantly elevated compared to normal tissues. GBM patients with higher transcriptional levels of CXCL5/6 were significantly associated with worse disease-free survival, while higher transcriptional levels of CXCL3/5/8 were significantly related to worse overall survival. The functions of CXC chemokines were enriched in Chemokine signaling pathway, Cytokine-cytokine receptor interaction, IL-17 signaling pathway, et.al. RELA and NFKB1were key transcription factors of CXC chemokines. The kinase targets of CXC chemokine contained CDK1, CDK2, PRKCD, MAPK14, ATM, LCK, MTOR, and GRK3, which are involved in oncogenesis, migration, and survival. Moreover, we revealed significant correlations between the expression of CXC chemokines and the infiltration immune cells, especially for dendritic cells.Conclusion The significant CXC chemokines and related pathways may provide a novel possibility for prognostic biomarkers and immunotherapeutic treatment in GMB.Short title: CXC Chemokines with prognosis in GBM

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A microporous roust La(III)-organic framework for cyanosilylation reactions and treatment effect on tuberculosis by activating the PI3K-AKT signaling pathway in immune cells

Arabian Journal of Chemistry ◽

10.1016/j.arabjc.2020.04.025 ◽

2020 ◽

Vol 13 (6) ◽

pp. 5890-5899

Author(s):

Liping Yan ◽

Qin Sun ◽

Zhibin Liu ◽

Min Wu ◽

Li Liang ◽

...

Keyword(s):

Signaling Pathway ◽

Immune Cells ◽

Treatment Effect ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Organic Framework

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Effect of Forsythiaside A on the RLRs Signaling Pathway in the Lungs of Mice Infected with the Influenza A Virus FM1 Strain

Molecules ◽

10.3390/molecules24234219 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4219

Author(s):

Xiao Zheng ◽

Yingjie Fu ◽

Shan-Shan Shi ◽

Sha Wu ◽

Yuqi Yan ◽

...

Keyword(s):

Retinoic Acid ◽

Signaling Pathway ◽

Influenza A Virus ◽

Immune Cells ◽

Influenza A ◽

T Cell Subsets ◽

Physical Parameters ◽

Gene And Protein Expression ◽

Forsythia Suspensa ◽

Inducible Gene

Forsythiaside A, a phenylethanoid glycoside monomer extracted from Forsythia suspensa, shows anti-inflammatory, anti-infective, anti-oxidative, and antiviral pharmacological effects. The precise mechanism underlying the antiviral action of forsythiaside A is not completely clear. Therefore, in this study, we aimed to determine whether the anti-influenza action of forsythiaside A occurs via the retinoic acid-inducible gene-I–like receptors (RLRs) signaling pathway in the lung immune cells. Forsythiaside A was used to treat C57BL/6J mice and MAVS−/− mice infected with mouse-adapted influenza A virus FM1 (H1N1, A/FM1/1/47 strain), and the physical parameters (body weight and lung index) and the expression of key factors in the RLRs/NF-κB signaling pathway were evaluated. At the same time, the level of virus replication and the ratio of Th1/Th2 and Th17/Treg of T cell subsets were measured. Compared with the untreated group, the weight loss in the forsythiaside A group in the C57BL/6J mice decreased, and the histopathological sections showed less inflammatory damage after the infection with the influenza A virus FM1 strain. The gene and protein expression of retinoic acid-inducible gene-I (RIG-I), MAVS, and NF-κB were significantly decreased in the forsythiaside A group. Flow cytometry showed that Th1/Th2 and Th17/Treg differentiated into Th2 cells and Treg cells, respectively, after treatment with forsythiaside A. In conclusion, forsythiaside A reduces the inflammatory response caused by influenza A virus FM1 strain in mouse lungs by affecting the RLRs signaling pathway in the mouse lung immune cells.

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Hepatitis C Virus Nonstructural Protein 5A Modulates the Toll-Like Receptor-MyD88-Dependent Signaling Pathway in Macrophage Cell Lines

Journal of Virology ◽

10.1128/jvi.00649-07 ◽

2007 ◽

Vol 81 (17) ◽

pp. 8953-8966 ◽

Cited By ~ 115

Author(s):

Takayuki Abe ◽

Yuuki Kaname ◽

Itsuki Hamamoto ◽

Yoshimi Tsuda ◽

Xiaoyu Wen ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Signaling Pathway ◽

Cell Lines ◽

Immune Cells ◽

Cytokine Production ◽

Toll Like Receptor ◽

Macrophage Cell ◽

Tlr Signaling ◽

Tlr Signaling Pathway

ABSTRACT Hepatitis C virus (HCV) infection induces a wide range of chronic liver injuries; however, the mechanism through which HCV evades the immune surveillance system remains obscure. Blood dendritic cells (DCs) play a pivotal role in the recognition of viral infection and the induction of innate and adaptive immune responses. Several reports suggest that HCV infection induces the dysfunction of DCs in patients with chronic hepatitis C. Toll-like receptor (TLR) has been shown to play various roles in many viral infections; however, the involvement of HCV proteins in the TLR signaling pathway has not yet been precisely elucidated. In this study, we established mouse macrophage cell lines stably expressing HCV proteins and determined the effect of HCV proteins on the TLR signaling pathways. Immune cells expressing NS3, NS3/4A, NS4B, or NS5A were found to inhibit the activation of the TLR2, TLR4, TLR7, and TLR9 signaling pathways. Various genotypes of NS5A bound to MyD88, a major adaptor molecule in TLR, inhibited the recruitment of interleukin-1 receptor-associated kinase 1 to MyD88, and impaired cytokine production in response to TLR ligands. Amino acid residues 240 to 280, previously identified as the interferon sensitivity-determining region (ISDR) in NS5A, interacted with the death domain of MyD88, and the expression of a mutant NS5A lacking the ISDR partially restored cytokine production. These results suggest that the expression of HCV proteins modulates the TLR signaling pathway in immune cells.

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