scholarly journals Phosphatase and Tensin Homolog Mutation in Immune Cell Infiltration and Clinicopathological Features of Low-Grade Gliomas

2020 ◽  
Vol 7 ◽  
Author(s):  
Peng Feng ◽  
Zhenqing Li ◽  
Yuchen Li ◽  
Yuelin Zhang
Keyword(s):  
Mrna Expression ◽  
Signaling Pathways ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Low Grade ◽  
Immune Cell Infiltration ◽  
Phosphatase And Tensin Homolog ◽  
Low Grade Gliomas ◽  
Tensin Homolog

The mutation of phosphatase and tensin homolog (PTEN) genes frequently occur in low-grade gliomas (LGGs) and are deeply associated with a poor prognosis and survival rate. In order to identify the crucial signaling pathways and genes associated with the PTEN mutation, we performed bioinformatics analysis on the RNA sequencing results, which were obtained from The Cancer Genome Atlas database. A total of 352 genes were identified as differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the DEGs were significantly enriched in categories associated with cell division and multiple metabolic progressions. The histological stage was significantly associated with PTEN expression levels. In addition, the PTEN mutation was associated with an abundance of B cells, neutrophils, macrophages, dendritic cells, and CD8+ T cells during tumor infiltration. The results showed that patients with LGGs harboring the PTEN mutation had a poor prognosis and more serious immune cell infiltration occurred depending on the mRNA expression level. These results demonstrated that multiple genes and signaling pathways play a key role in LGG from low grade to high grade, and are associated with PTEN mutations. In this study, we outlined an approach to assess the influence of PTEN mutations on prognosis, overall survival, and messenger RNA (mRNA) expression. Our results provided alternative strategies for the personalized treatment of patients with LGGs harboring the PTEN mutation.

scholarly journals Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

2022 ◽  
Vol 12 ◽  
Author(s):  
Chenlu Li ◽  
Jingjing Pan ◽  
Yinyan Jiang ◽  
Yan Yu ◽  
Zhenlin Jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Signaling Pathways ◽  
Poor Prognosis ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Therapeutic Responses

Background: Gastric cancer (GC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable indices especially immunotherapy-associated parameters that can predict the therapeutic responses to immunotherapy of GC patients.Methods: Gene expression profile of 854 GC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE84433) with their corresponding clinical and somatic mutation data. Based on immune cell infiltration (ICI) levels, molecular clustering classification was performed to identify subtypes and ICI scores in GC patients. After functional enrichment analysis of subtypes, we further explored the correlation between ICI scores and Tumor Mutation Burden (TMB) and the significance in clinical immunotherapy response.Results: Three subtypes were identified based on ICI scores with distinct immunological and prognostic characteristics. The ICI-cluster C, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration and up-regulation of PD-L1. ICI scores were identified through using principal component analysis (PCA) and the low ICI scores were consistent with the increased TMB and the immune-activating signaling pathways. Contrarily, the high-ICI score cluster was involved in the immunosuppressive pathways, such as TGF-beta, MAPK and WNT signaling pathways, which might be responsible for poor prognosis of GC. External immunotherapy and chemotherapy cohorts validated the patients with lower ICI scores exhibited significant therapeutic responses and clinical benefits.Conclusion: This study elucidated that ICI score could sever as an effective prognostic and predictive indicator for immunotherapy in GC. These findings indicated that the systematic assessment of tumor ICI landscapes and identification of ICI scores have crucial clinical implications and facilitate tailoring optimal immunotherapeutic strategies.

scholarly journals Bioinformatics Analysis of C3 in Brain Low Grade Gliomas as Potential Therapeutic Target and Promoting Immune Cell Infiltration

2021 ◽  
Author(s):  
Xiujuan wu ◽  
Siyi Wu ◽  
Kaiting Miao ◽  
Lijing Wang ◽  
Yuanyuan Ma
Keyword(s):  
Cell Cycle ◽  
Immune Cell ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Low Grade ◽  
Immune Cell Infiltration ◽  
Mesenchymal Transition ◽  
Low Grade Gliomas ◽  
Regulation Of Cell Cycle ◽  
The Impact

Abstract Background Low grade gliomas is the malignant nervous tumor with distinct biological and clinical characteristics. Despite advances in diagnostic and therapeutic methods, how to significantly elongate the survival of low grade gliomas is still the challenge. Complement 3, as the critical component in the innate immune system, play an essential role in local immune response and participated into the regulation of the epithelial-mesenchymal transition and tumor microenvironment. Methods In this study, we systematically determined the expression levels of C3 in low grade gliomas using various public databases. Then, we further identified the impact of C3 expression on immune cell infiltration compared to normal tissue, indicating the effect of cellular microenvironment on overall survival of LGG patients. Results We obtained transcriptional and survival of C3 in LGG from GEPIA and cBioportal database, and the differentially expressed genes were obtained. By performing the analysis of GO and protein-protein interaction network, we have identified the top-ranked 10 hub genes, which are highly associated with regulation of cell cycle. The gene set enrichment analysis demonstrated that overexpression of C3 in LGG patient is positively correlated with regulation of cell cycle. Finally, the immune cell infiltration of C3 in LGG patients was employed and clearly showed that higher neutrophil infiltration can worsen the survival of LGG patients with higher C3 expression. These results were confirmed by the Human Protein Atlas database, in which expression level of C3 protein in gliomas patients always higher. Conclusions This investigation implied that C3 can be as the potential targets of precise therapy for patient with low grade gliomas.

scholarly journals Neuropilin1 Expression Acts as a Prognostic Marker in Stomach Adenocarcinoma by Predicting the Infiltration of Treg Cells and M2 Macrophages

2020 ◽  
Vol 9 (5) ◽  
pp. 1430 ◽  
Author(s):  
Ji Young Kang ◽  
Minchan Gil ◽  
Kyung Eun Kim
Keyword(s):  
Mrna Expression ◽  
Clinical Relevance ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Treg Cells ◽  
Cell Infiltration ◽  
M2 Macrophage ◽  
Immune Cell Infiltration ◽  
Stomach Adenocarcinoma

Neuropilin1 (NRP1) plays a critical role in tumor progression and immune responses. Although the roles of NRP1 in various tumors have been investigated, the clinical relevance of NRP1 expression in stomach adenocarcinoma (STAD) has not been studied. To investigate the use of NRP1 as a prognostic biomarker of STAD, we analyzed NRP1 mRNA expression and its correlation with patient survival and immune cell infiltration using various databases. NRP1 mRNA expression was significantly higher in STAD than normal tissues, and Kaplan-Meier survival analysis showed that NRP1 expression was significantly associated with poor prognosis in patients with STAD. To elucidate the related mechanism, we analyzed the correlation between NRP1 expression and immune cell infiltration level. In particular, the infiltration of immune-suppressive cells, such as regulatory T (Treg) cells and M2 macrophage, was significantly increased by NRP1 expression. In addition, the expression of interleukin (IL)-35, IL-10, and TGF-β1 was also positively correlated with NRP1 expression, resulting in the immune suppression. Collectively in this study, our integrated analysis using various clinical databases shows that the significant correlation between NRP1 expression and the infiltration of Treg cells and M2 macrophage explains poor prognosis mechanism in STAD, suggesting the clinical relevance of NRP1 expression as a prognostic biomarker for STAD patients.

scholarly journals Identification of SHMT2 as a Potential Prognostic Biomarker and Correlating with Immune Infiltrates in Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lianxiang Luo ◽  
Yushi Zheng ◽  
Zhiping Lin ◽  
Xiaodi Li ◽  
Xiaoling Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mrna Expression ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Methyl Transferase ◽  
Cox Proportional Hazard Regression

It has attracted growing attention that the role of serine hydroxy methyl transferase 2 (SHMT2) in various types of cancers. However, the prognostic role of SHMT2 in lung adenocarcinoma (LUAD) and its relationship with immune cell infiltration is not clear. In this study, the information of mRNA expression and clinic data in LUAD were, respectively, downloaded from the GEO and TCGA database. We conducted a biological analysis to select the signature gene SHMT2. Online databases including Oncomine, GEPIA, TISIDB, TIMER, and HPA were applied to analyze the characterization of SHMT2 expression, prognosis, and the correlation with immune infiltration in LUAD. The mRNA expression and protein expression of SHMT2 in LUAD tissues were higher than in normal tissue. A Kaplan-Meier analysis showed that patients with lower expression level of SHMT2 had a better overall survival rate. Multivariate analysis and the Cox proportional hazard regression model revealed that SHMT2 expression was an independent prognostic factor in patients with LUAD. Meanwhile, the gene SHMT2 was highly associated with tumor-infiltrating lymphocytes in LUAD. These results suggest that the SHMT2 gene is a promising candidate as a potential prognostic biomarker and highly associated with different types of immune cell infiltration in LUAD.

scholarly journals Identification of Autophagy-Related Prognostic Signature and Analysis of Immune Cell Infiltration in Low-Grade Gliomas

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Qingli Quan ◽  
Xinxin Xiong ◽  
Shanyun Wu ◽  
Meixing Yu
Keyword(s):  
Risk Score ◽  
Immune Cells ◽  
Roc Analysis ◽  
Immune Cell ◽  
Time Dependent ◽  
Low Grade ◽  
Immune Cell Infiltration ◽  
Prognostic Signature ◽  
Low Grade Gliomas ◽  
Key Genes

Autophagy plays an important role in cancer. Many studies have demonstrated that autophagy-related genes (ARGs) can act as a prognostic signature for some cancers, but little has been known in low-grade gliomas (LGG). In our study, we aimed to establish a prognostical model based on ARGs and find prognostic risk-related key genes in LGG. In the present study, a prognostic signature was constructed based on a total of 8 ARGs (MAPK8IP1, EEF2, GRID2, BIRC5, DLC1, NAMPT, GRID1, and TP73). It was revealed that the higher the risk score, the worse was the prognosis. Time-dependent ROC analysis showed that the risk score could precisely predict the prognosis of LGG patients. Additionally, four key genes (TGFβ2, SERPING1, SERPINE1, and TIMP1) were identified and found significantly associated with OS of LGG patients. Besides, they were also discovered to be strongly related to six types of immune cells which infiltrated in LGG tumor. Taken together, the present study demonstrated the promising potential of the ARG risk score formula as an independent factor for LGG prediction. It also provided the autophagy-related signature of prognosis and potential therapeutic targets for the treatment of LGG.

scholarly journals Distinct Expression Pattern and Prognostic Values of E2F Family Genes in Lung Adenocarcinoma and Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Shuo Wang ◽  
Jun Zhang ◽  
Fan-Jie Meng ◽  
Yi-Jie Yan ◽  
Bin Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Single Cell ◽  
Expression Pattern ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Immune Cell Infiltration ◽  
The Poor

Abstract The E2F transcription factors family included E2F1-8 playing the crucial roles in the origination and progression of various kinds of human cancers. However, a comprehensive analysis regarding the gene mRNA expression pattern at bulk and single-cell resolution, the prognostic values and the association to immune cell infiltration of E2F family genes in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) remains to be performed. The bulk and single-cell mRNA expression levels of E2F family members in LUAD and LUSC were determined using the cBioPortal, Gepia, TISCH and Oncomine online databases. Based on the differentially expressed genes, GO enrichment and GSEA items were investigated. The Kaplan‑Meier plotter server was used to evaluate the prognostic significances of the E2F family genes in patients with LUAD and LUSC based on the related clinicopathological features. The correlation between E2F family gene expression and immune cell infiltration was explored using the Timer database. Our bulk and single-cell RNA analyses revealed that E2F1, E2F2 and E2F8 might promote the tumor growth and aggressiveness of LUAD and LUSC indicating the poor prognosis prediction. E2F4 and E2F6 might be considered as the potential outcome markers for the improved treatment of LUAD and LUSC, respectively. Upregulation of E2F1 and E2F8 indicated the poor prognosis of LUAD patients, whereas only E2F2 overexpression was associated with shorter overall survival of LUSC patients. There existed a positive relationship between E2F8 expression level and infiltration level of macrophages and DCs, and significantly positive correlation between infiltration level of CD8+ T, CD4+ T cells and E2F1/2/7 expression in LUAD and LUSC. In conclusion, our findings suggested that increased expression of E2F1/E2F8 or E2F2 may serve as promising prognostic biomarkers for patients with LUAD or LUSC, respectively.

scholarly journals CXCL5 overexpression predicts a poor prognosis in pancreatic ductal adenocarcinoma and is correlated with immune cell infiltration

2020 ◽  
Vol 11 (9) ◽  
pp. 2371-2381 ◽  
Author(s):  
Ronghua Zhang ◽  
Qiaofei Liu ◽  
Junya Peng ◽  
Mengyi Wang ◽  
Tong Li ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Ductal Adenocarcinoma ◽  
Immune Cell Infiltration

scholarly journals Prevention of lipopolysaccharide-induced CD11b+ immune cell infiltration in the kidney: role of AT2 receptors

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Sanket Patel ◽  
Isha Dhande ◽  
Elizabeth Alana Gray ◽  
Quaisar Ali ◽  
Tahir Hussain
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Interleukin 10 ◽  
Conditioned Media ◽  
Cell Infiltration ◽  
Low Grade ◽  
Immune Cell Infiltration ◽  
Anti Inflammatory

AbstractImmune cell infiltration plays a central role in mediating endotoxemic acute kidney injury (AKI). Recently, we have reported the anti-inflammatory and reno-protective role of angiotensin-II type-2 receptor (AT2R) activation under chronic low-grade inflammatory condition in the obese Zucker rat model. However, the role of AT2R activation in preventing lipopolysaccharide (LPS)-induced early infiltration of immune cells, inflammation and AKI is not known. Mice were treated with AT2R agonist C21 (0.3 mg/kg), with and without AT2R antagonist PD123319 (5 mg/kg) prior to or concurrently with LPS (5 mg/kg) challenge. Prior-treatment with C21, but not concurrent treatment, significantly prevented the LPS-induced renal infiltration of CD11b+ immune cells, increase in the levels of circulating and/or renal chemotactic cytokines, particularly interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) and markers of renal dysfunction (blood urea nitrogen and albuminuria), while preserving anti-inflammatory interleukin-10 (IL-10) production. Moreover, C21 treatment in the absence of LPS increased renal and circulating IL-10 levels. To investigate the role of IL-10 in a cross-talk between epithelial cells and monocytes, we performed in vitro conditioned media (CM) studies in human kidney proximal tubular epithelial (HK-2) cells and macrophages (differentiated human monocytes, THP-1 cells). These studies revealed that the conditioned-media derived from the C21-treated HK-2 cells reduced LPS-induced THP-1 tumor necrosis factor-α (TNF-α) production via IL-10 originating from HK-2 cells. Our findings suggest that prior activation of AT2R is prophylactic in preventing LPS-induced renal immune cell infiltration and dysfunction, possibly via IL-10 pathway.

scholarly journals MODL-11. COMPARISON OF HUMAN & MURINE PA/PXA CHARACTERISTICS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii413-iii413
Author(s):  
Alexander C Sommerkamp ◽  
Pengbo Sun ◽  
Annika K Wefers ◽  
Britta Ismer ◽  
Kathrin Schramm ◽  
...  
Keyword(s):  
Immune Cell ◽  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e ◽  
Cell Infiltration ◽  
Low Grade ◽  
Immune Cell Infiltration ◽  
Preclinical Research ◽  
Who Grade ◽  
Pediatric Tumor ◽  
Tumor Types

Abstract Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. Despite recent advances in the molecular characterization of this heterogeneous set of tumors, the separation of specific tumor types is still not fully established. Pilocytic astrocytoma (PA; WHO grade I) and pleomorphic xanthoastrocytoma (PXA; WHO grade II) are two pLGG types that can be difficult to distinguish based on histology alone. Even though their clinical course is different, they are often grouped as ‘pLGG’ in clinical trials (and therefore treated similarly). Based on a cohort of 89 human pediatric tumor samples, we show that PAs and PXAs have clearly distinct methylation and transcriptome profiles. The difference in gene expression is mainly caused by cell cycle- and development-associated genes, suggesting a key difference in the regulatory circuits involved in tumor growth. In addition to BRAF V600E, we found NTRK fusions and a previously unknown EGFR:BRAF fusion as mutually exclusive driving events in PXAs. Both tumor types show marked signs of immune cell infiltration, but with significant qualitative differences, which might represent therapeutic vulnerabilities. To pave the way for further research on PA and PXA, we developed corresponding mouse models using the virus-based RCAS system, which allows introduction of an oncogenic driver into immunocompetent mice for molecular and preclinical research. The murine tumors do not only histologically resemble their human counterparts but also show a similar growth behavior. Expression analysis revealed that the murine PXAs have a stronger gene signature of proliferation and immune cell infiltration compared to PAs.

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