scholarly journals Integrative Analysis of Gene Expression Based on Multi-Omics Databases Identified CXC Chemokines as Immune Prognostic Biomarkers of Rectal Adenocarcinoma

2021 ◽  
Author(s):  
Xiaoshuai Wang ◽  
Zhiyang Hu ◽  
Zefeng Du ◽  
Dongchun Hong ◽  
Haoyang Huang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Rectal Adenocarcinoma ◽  
Clinicopathological Features ◽  
Prognostic Biomarkers ◽  
Regulatory Mechanisms ◽  
High Recurrence Rate ◽  
Poor Survival ◽  
Lower Expression ◽  
Cell Chemotaxis

Abstract Background: Rectal adenocarcinoma (READ) is one of the most frequent malignancies with a high recurrence rate. CXC chemokines, as indispensable components of the immune system, are considered broadly involving in tumorigenesis by orchestrating the immune cell chemotaxis and thus affect the prognosis of READ patients. However, the values of CXC chemokines as prognostic biomarkers and potential regulatory mechanisms for READ remain unclear.Results: The expression levels of CXCL3, CXCL12, and CXCL13 were aberrant in both TCGA and ONCOMINE databases. Lower expression of CXCL3 and CXCL13 predicted poor survival of READ patients. Additionally, both CXCL3 and CXCL13 were associated with several clinicopathological features. CXCL3 and CXCL13 expressions were significantly correlated with the tumor infiltration levels of immune cells in READ tissue. CeRNA networks of mRNA-miRNA-lncRNA were constructed to reveal the potential mechanisms that regulated the expressions of CXCL3 and CXCL13. Furthermore, GSEA revealed the association between immune-related pathways and CXCL3 as well as CXCL13.Conclusions: CXCL3 and CXCL13 could be valuable prognostic biomarkers in READ. CXCL3/miR-425-5p/chr22-38_28785274–29006793.1 was identified as the most potential ceRNA network in READ. Our results might provide novel insights in READ immunotherapy.

scholarly journals A dual immune signature of CD8+ T Cells and MMP9 improves the survival of hepatocellular carcinoma patients

2021 ◽  
Author(s):  
Huan Ding ◽  
Huan Hu ◽  
Feifei Tian ◽  
Huaping Liang
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Cox Regression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
High Recurrence Rate ◽  
Immune Signature

The 5-year survival of hepatocellular carcinoma (HCC) is difficult due to the high recurrence rate and metastasis. Tumor infiltrating immune cells (TICs) and immune-related genes (IRGs) bring hope to improve survival and treatment of HCC patients. However, there are problems in predicting immune signatures and identifying novel therapeutic targets. In the study, the CIBERSORT algorithm was used to evaluate 22 immune cell infiltration patterns in gene expression omnibus (GEO) and the cancer genome atlas (TCGA) data. Eight immune cells were found to have significant infiltration differences between the tumor and normal groups. The CD8+ T Cells immune signature was constructed by least absolute shrinkage and selection operator (LASSO) algorithm. The high infiltration level of CD8+ T Cells could significantly improve survival of patients. The weighted gene co-expression network analysis (WGCNA) algorithm identified MMP9 was closely related to the overall survival of HCC patients. K-M survival and tROC analysis confirmed that MMP9 had an excellent prognostic prediction. Cox regression showed that a dual immune signature of CD8+ T Cells and MMP9 was independent survival factor in HCC. Therefore, a dual prognostic immune signature could improve the survival of patient and may provide a new strategy for the immunotherapy of HCC.

scholarly journals 1 Dissecting β-catenin associated inflammation in patients with desmoid fibromatosis to identify prognostic biomarkers

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A1-A1
Author(s):  
Laura Bergamaschi ◽  
Federica Perrone ◽  
Francesca Rini ◽  
Licia Rivoltini ◽  
Chiara Castelli ◽  
...  
Keyword(s):  
Active Surveillance ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Prognostic Biomarkers ◽  
Molecular Profile ◽  
High Recurrence Rate ◽  
Desmoid Fibromatosis ◽  
Inflammatory Status ◽  
Functional Features ◽  
Promising Source

BackgroundDesmoid fibromatosis (DF) is a locally aggressive rare tumor with high recurrence rate after surgery and unpredictable clinical course. Standard of care for DF patients is active surveillance; however, 30% of patients will progress and need active treatments. Biomarkers discriminating aggressive forms of DF are not available and prediction of progressing patients remains challenging. DF harbors mutations in β-catenin and a transcriptional ‘inflammatory phenotype’. Cancer-associated inflammation is fostered by systemic factors and detectable in circulating immune cells. Blood leukocytes thus represent a promising source of prognostic biomarkers for DF patients. In this study we investigate phenotypic and functional features of peripheral blood immune cells and molecular profile of DF biopsies to identify DF patients at risk of progression and guide tailored therapeutic approaches.MethodsThis is a prospective observational study enrolling patients with primary sporadic desmoid fibromatosis under active surveillance (n=80). Tumor and blood samples collected at diagnosis and during active surveillance will be studied by 1. transcriptomic analysis of DF biopsies; 2. multiparametric flowcytometry and functional profiling of blood cells; 3. RNA profiling of whole blood; 4. evaluation of plasma levels of cyto/chemokine and ctDNA of β-catenin variants. Levels of blood analytes will be correlated with patients‘ clinical outcome and integrated with immunological parameters.ResultsPeripheral blood immune profile of 42 cases and 17 healthy donors (HD) shows that DF patients display at baseline an altered myeloid profile compared to HD, which is maintained in a subset of patients during the first year of active surveillance. An increase in immunosuppressive activated granulocytes and granulocytic myeloid-derived suppressor cells, defined by differential co-expression of CD15, CD11b, CD16 and LOX1, is observed, concomitantly, with a boost of monocyte subsets, defined by co-expression of CD33, CD11b, CD14, CD16, HLA-DR and PDL1. Immunosuppressive low density granulocytes are increased in progressing patients compared to HD and regressors. Of note, a significant up-regulation of immunosuppressive PMN-MDSC (defined as CD15+LOX-1+) is observed in DF harboring T41A mutation, but not in S45 mutated DF.Transcriptomic data of DF biopsies and of plasma analytes are ongoing.ConclusionsSystemic alterations of immunosuppressive and inflammatory myeloid cell subsets in peripheral blood of DF patients indicate that the inflammatory status detected at tumor site is reflected at systemic level. The altered myeloid profile supports the involvement of the immune system in DF onset and may represent a marker of disease aggressiveness.AcknowledgementsSupported by Italian Ministry of Health (RF-2016-02362609).Trial RegistrationNot applicable.ReferencesNot applicable.Ethics ApprovalThe study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (protocol code INT85/10).ConsentWritten informed consent was obtained from the patient for publication of this abstract. A copy of the written consent is available for review by the Editor of this journal.

scholarly journals Analysis of Therapeutic Targets and Prognostic Biomarkers of CXC Chemokines in Cervical Cancer Microenvironment

2021 ◽  
Author(s):  
Wei na Kong ◽  
Gang Zhao ◽  
Hai xia Chen ◽  
Wei na Wang ◽  
Xiao qian Shang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Activity ◽  
Comprehensive Analysis ◽  
Prognostic Biomarkers ◽  
Quantitative Real Time Pcr ◽  
Cell Transport ◽  
Selection Of

Abstract Background: It is well known that the tumor microenvironment (TME) has been received an increasing number of attention. CXC chemokines could regulate immune cell transport and tumor cell activity, thus exerting anti-tumor immunity. However, studies on the expression and prognosis of CXC chemokines in cervical cancer (CC) are more limited. Methods: The study investigated the role of CXC chemokines in the TME and prognosis of CC using public databases. Moreover, quantitative real-time PCR (Q-PCR) and immunohistochemistry (IHC) of CXC chemokines were performed to further verify. Results: The transcriptional levels of CXCL1/3/5/6/8/9/10/11/13/14/16/17 in CC tissues were significantly elevated while the transcriptional levels of CXCL2/4/7/12 were significantly reduced. We reached a consistent conclusion that the expression of CXCL9/10/11/13 was verified by Q-PCR and IHC. Moreover, CC patients with low transcriptional levels of CXCL1/2/3/4/5/8 were signifi-cantly associated with longer overall survival (OS). Our data suggest that RELA, NFKB1, and SP1 are key transcription factors for CXC chemokines, and the LCK, LYN and PAK are CXC chemokine kinases targets. We found significant correlations among the expression of CXC chemokines and the infiltration of six types of immune cells. Conclusions: We performed a comprehensive analysis of CXC chemokines via clinical data and some online tumor database. Our results may provide new idea for the selection of immunotherapeutic targets and prognostic biomarkers for cervical cancer.

scholarly journals Cell Volume Regulation in Immune Cell Function, Activation and Survival

2021 ◽  
Vol 55 (S1) ◽  
pp. 71-88
Keyword(s):  
Ion Channels ◽  
Ion Transport ◽  
Cell Volume ◽  
Immune Cells ◽  
Volume Regulation ◽  
Cell Function ◽  
Immune Cell ◽  
Regulatory Mechanisms ◽  
Immune Cell Function ◽  
Volume Decrease

The regulation of cell volume is an essential cellular process in nearly every living organism. The importance of volume regulation in immune cells cannot be understated, as it ensures proper cellular function and effective immune response. These cells utilize ion channels and transporters to maintain volume homeostasis through rapid ion transport across the cell membrane. Immune cells express mechanisms controlling regulatory volume decrease (RVD), regulatory volume increase (RVI), proliferative RVD, and apoptotic volume decrease (AVD). In this review, we summarize recent studies examining the importance of several ion channels, particularly potassium and chloride channels in regulating ion transport during osmotic stress, and in immune cell function, activation, proliferation, and death. We also review the key mechanisms functioning in immune cell proliferation and apoptosis. They serve a crucial role in maintaining adequate ionic concentrations, mediating immune cell activation, and generating proliferative pathways. These regulatory mechanisms play key roles in the function and survival of immune cells, as impaired volume regulation contributes to the pathophysiology of various disorders. A complete understanding of immune cell volume regulatory mechanisms may be a starting point for the development of therapeutic agents targeting these ion channels to treat inflammatory diseases.

scholarly journals Analysis of Therapeutic Targets and Prognostic Biomarkers Among semaphorins in the glioblastoma Microenvironment

2021 ◽  
Author(s):  
Fan Jiang ◽  
Yanbo Yang ◽  
Zilan Wang ◽  
Guangjie Liu ◽  
Xiaohong Du ◽  
...  
Keyword(s):  
Target Genes ◽  
Synapse Formation ◽  
Neural Circuits ◽  
Immune Cell ◽  
Prognostic Biomarkers ◽  
Normal Brain ◽  
Poor Survival ◽  
Supply Potential ◽  
Tcga Dataset ◽  
Selection Of

Abstract Background Glioblastoma (GBM) is the most invasive and common form among brain cancers in adults. GBM is characterized for its poor survival and markedly high tumors heterogeneity with shortage of effective therapies. Semaphorins, a family of membrane-associated and secreted proteins, were originally defined as neuronal growth pyramidal proteins involved in directing repulsive axons. Semaphorins are repeatedly involved in the evolution of neural circuits, involving not only the generation and guidance of neurons, but also the recognition of target regions and cells and synapse formation. However, the differential expression and clinical prognostic value of semaphorins in GBM were not yet available clarity. Methods In this study, various databases including ONCOMINE (1159 samples), GEPIA (TCGA and GTEx dataset), UALCAN (samples from TCGA dataset), cBioPortal (604 samples from GDAC firehose of TCGA dataset), GeneMANIA(data from publicly available daatbases, e.g. GEO, BioGRID) and TIMER(samples from TCGA) were exploited. Results We found that in GBM tissues the transcriptional levels of SEMA3A/3B/3E/3F/5A/6A were markedly elevated, while those of SEMA3G/4A/4D/4F/5B were markedly reduced. GBM patients with lower levels of SEMA3F/4F transcription had a significantly better outcome. The function of semaphorins was mainly related to the regulation of cell growth and development. Besides, we found that the expression of semaphorin was significantly correlated with the infiltration of immune cells. Conclusions Semaphroins are differentially expressed in glioblastoma compared with normal brain tissue. They could provide diverse prognostic values, participate in various molecular pathways. In addition, the semaphorin protein family plays an important role in immune cell infiltration. Our study may supply potential target genes for the treatment of glioblastoma while providing new insights into the selection of prognostic biomarkers. Besides, our results may offer new insights into immunotherapy targeting and analysis of protein co-expression in SEMA for glioblastoma.

scholarly journals Stress Granules in the Post-transcriptional Regulation of Immune Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Nicolas Curdy ◽  
Olivia Lanvin ◽  
Sarah Cadot ◽  
Camille Laurent ◽  
Jean-Jacques Fournié ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Immune Cells ◽  
Messenger Rna ◽  
Cell Activation ◽  
Immune Cell ◽  
Current Knowledge ◽  
Stress Granules ◽  
Regulatory Mechanisms ◽  
Ribonucleoprotein Complexes ◽  
Post Transcriptional Regulation

Immune cell activation triggers transcriptional and translational programs eliciting cellular processes, such as differentiation or proliferation, essential for an efficient immune response. These dynamic processes require an intricate orchestration of regulatory mechanisms to control the precise spatiotemporal expression of proteins. Post-transcriptional regulation ensures the control of messenger RNA metabolism and appropriate translation. Among these post-transcriptional regulatory mechanisms, stress granules participate in the control of protein synthesis. Stress granules are ribonucleoprotein complexes that form upon stress, typically under control of the integrated stress response. Such structures assemble upon stimulation of immune cells where they control selective translational programs ensuring the establishment of accurate effector functions. In this review, we summarize the current knowledge about post-transcriptional regulation in immune cells and highlight the role of stress sensors and stress granules in such regulation.

scholarly journals Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
De-Chen Yu ◽  
Xiang-Yi Chen ◽  
Xin Li ◽  
Hai-Yu Zhou ◽  
De-Quan Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Complex ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Prognostic Biomarkers ◽  
High Expression

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.

scholarly journals Reclassification of Kidney Clear Cell Carcinoma Based on Immune Cell Gene-Related DNA CpG Pairs

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 215
Author(s):  
Qizhan Luo ◽  
Thomas-Alexander Vögeli
Keyword(s):  
Cell Carcinoma ◽  
Immune Cell ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Pairwise Comparison ◽  
Clinicopathological Features ◽  
Immune Checkpoints ◽  
Potential Mechanism ◽  
Tissue Samples

Background: A new method was developed based on the relative ranking of gene expression level, overcoming the flaw of the batch effect, and having reliable results in various studies. In the current study, we defined the two methylation sites as a pair. The methylation level in a specific sample was subject to pairwise comparison to calculate a score for each CpGs-pair. The score was defined as a CpGs-pair score. If the first immune-related CpG value was higher than the second one in a specific CpGs-pair, the output score of this immune-related CpGs-pair was 1; otherwise, the output score was 0. This study aimed to construct a new classification of Kidney Clear Cell Carcinoma (KIRC) based on DNA CpGs (methylation sites) pairs. Methods: In this study, the biomarkers of 28 kinds of immune infiltration cells and corresponding methylation sites were acquired. The methylation data were compared between KIRC and normal tissue samples, and differentially methylated sites (DMSs) were obtained. Then, DNA CpGs-pairs were obtained according to the pairs of DMSs. In total, 441 DNA CpGs-pairs were utilized to construct a classification using unsupervised clustering analysis. We also analyzed the potential mechanism and therapy of different subtypes, and validated them in a testing set. Results: The classification of KIRC contained three subgroups. The clinicopathological features were different across three subgroups. The distribution of immune cells, immune checkpoints and immune-related mechanisms were significantly different across the three clusters. The mutation and copy number variation (CNV) were also different. The clinicopathological features and potential mechanism in the testing dataset were consistent with those in the training set. Conclusions: Our findings provide a new accurate and stable classification for developing personalized treatments for the new specific subtypes.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyösti Tahkola ◽  
Maarit Ahtiainen ◽  
Jukka-Pekka Mecklin ◽  
Ilmo Kellokumpu ◽  
Johanna Laukkarinen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Geographical Area ◽  
Prognostic Significance ◽  
Staining Intensity ◽  
Ductal Adenocarcinoma ◽  
Poor Survival ◽  
Negative Prognostic Factor ◽  
High Level ◽  
Immune Cell Score

AbstractHyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.

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