scholarly journals Construction of Immune-related lncRNA Prognosis Models and Development Related Networks and Drugs in LGG

2021 ◽  
Author(s):  
Xiaoyu Zhang ◽  
Xiaoqin He ◽  
Lin Xiong ◽  
Yangtao Xu ◽  
Wenliang Chen ◽  
...  
Keyword(s):  
Immune Cells ◽  
Prognostic Significance ◽  
Clinical Staging ◽  
Lower Grade ◽  
Lasso Regression ◽  
Malignant Tumours ◽  
Lower Grade Glioma ◽  
Patient Prognosis ◽  
Core Genes

Abstract Glioma is the most important tumor of the nervous system. LncRNA plays an important role in the occurrence, development, and metastasis of glioma. The immune status of glioma plays an important role in its treatment and prognosis. In lower-grade glioma (LGG), based on the results of the Weighted correlation network analysis (WCGNA) of lncRNA, we used lasso regression, random forest model, and stepwise regression to establish the lncRNA prognostic model: 0.58349*CYTOR + 0. 47804*LINC01831 + 0. 24933*HOTAIRM1 + 0. 73600*AC022034 + 0. 62351*AC104407 = lncRNA model prognosis score (LMPS). Concomitantly, we explored the correlation of LMPS with the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE), Tumor IMmune Estimation Resource (TIMER) infiltrating immune cells. We also established the reciprocal network of the model and verified the significant prognostic significance of the hub genes of the network and the significant impact on immunity. Finally, by connectivity Map (cMap) analysis, we obtained the drugs about the WCGNA module where the model is. Our study highlights the close role of the lncRNA model with patient prognosis, immunity, and clinical staging, and can guide immunotherapy. The network is constructed with the model as the core. Its core genes also have a guiding role in patient prognosis, immunity, and treatment. We identified loratadine and fidaxomicin as possible drugs.

The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽  
2021 ◽  
Author(s):  
Peng Wang ◽  
Chen Luo ◽  
Peng-jie Hong ◽  
Wen-ting Rui ◽  
Shuai Wu
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Lower Grade ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Lower Grade Glioma ◽  
Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

Prognostic and immune roles of synaptotagmin-4 in gastric cancer and brain lower-grade glioma

2020 ◽  
Author(s):  
Siyuan Jiang ◽  
Lizhe Zhu ◽  
Chao Jiang ◽  
Shibo Yu ◽  
Bin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Cells ◽  
Treg Cells ◽  
Lower Grade ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Lower Grade Glioma ◽  
Close Relationship ◽  
Human Protein Atlas ◽  
The Relationship

Abstract Background Synaptotagmins (SYTs) are a family of proteins whose primary function is serving as a calcium sensor in vesicle transport and exocytosis, playing an important role in the function of immune cells. There is also a close relationship between immune cells and tumours. SYT4 is one molecule involved in this relationship, but the relationship between SYT4 and cancer remains unclear. Therefore, we hypothesize that SYT4 can affect the prognosis of cancer, and may be related to immune cells. Methods The following databases were used to study the immunological and prognostic role of SYT4 in cancers: Oncomine, Kaplan-Meier plotter, The Human Protein Atlas, CCLE, GEPIA2, TIMER, and CGGA. Results SYT4 expressions were lower in many cancers than in normal tissues. Specifically in gastric cancer and lower-grade gliomas, SYT4 played a protective and harmful role, respectively. Moreover, a difference between SYT4 expression and the levels of immune infiltration existed in stomach adenocarcinoma (STAD) and brain lower-grade glioma (LGG). In addition, we found that the relationship between markers of monocytes, M1 and M2 macrophages, tumour-associated macrophages (TAMs), Treg cells, B lymphocytes, dendritic cells (DCs) and SYT4 expression was opposite in STAD and LGG. Conclusions The effect of SYT4 on the prognosis of patients with STAD and LGG was opposite. And SYT4 has different effects on immune infiltration in these two tumours. Therefore, SYT4 might be a potential prognostic and tumour immune-related biomarker in STAD and LGG.

scholarly journals NLGN3 Upregulates Expression of ADAM10 to Promote the Cleavage of NLGN3 via Activating the LYN Pathway in Human Gliomas

2021 ◽  
Vol 9 ◽  
Author(s):  
Ning-Ning Dang ◽  
Xiao-Bing Li ◽  
Mei Zhang ◽  
Chen Han ◽  
Xiao-Yong Fan ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Feedback Regulation ◽  
Feedback Mechanism ◽  
Therapeutic Window ◽  
Migration And Invasion ◽  
Lower Grade ◽  
Lower Grade Glioma ◽  
Glioma Growth ◽  
The Brain

The neuron derived synaptic adhesion molecular neuroligin-3 (NLGN3) plays an important role in glioma growth. While the role of autocrine NLGN3 in glioma has not been well-studied. The expression of NLGN3 in glioma was detected using immunohistochemistry. We further explored its function and regulatory mechanism in U251 and U87 cells with high expression of NLGN3. Knockdown of endogenous NLGN3 significantly reduced the proliferation, migration, and invasion of glioma cells and down-regulated the activity of the PI3K-AKT, ERK1/2, and LYN signaling pathways. In comparison, overexpression of NLGN3 yielded opposite results. Our results further demonstrate that LYN functions as a feedback mechanism to promote NLGN3 cleavage. This feedback regulation was achieved by upregulating the ADAM10 sheddase responsible for NLGN3 cleavage. Inhibition of ADAM10 suppressed the proliferation, migration, and invasion of glioma cells; oppositely, the expression of ADAM10 was correlated with a higher likelihood of lower grade glioma (LGG) in the brain. Our study demonstrates that glioma-derived NLGN3 promotes glioma progression by upregulating activity of LYN and ADAM10, which in turn promote NLGN3 cleavage to form a positive feedback loop. This pathway may open a potential therapeutic window for the treatment of human glioma.

scholarly journals T-Cell Exhaustion Status Under High and Low Levels of Hypoxia-Inducible Factor 1α Expression in Glioma

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai Liu ◽  
Xing Liu ◽  
Chuanbao Zhang ◽  
Wei Shan ◽  
Xiaoguang Qiu
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cells ◽  
Hypoxia Inducible Factor ◽  
Lower Grade ◽  
T Cell Exhaustion ◽  
Expression Levels ◽  
Cell Exhaustion ◽  
Lower Grade Glioma ◽  
Genome Atlas

Background: Hypoxia-inducible factor 1α (HIF1A), the principal regulator of hypoxia, is involved in the suppression of antitumor immunity. We aimed to describe the T-cell exhaustion status of gliomas under different levels of HIF1A expression.Methods: In this study, 692 patients, whose data were collected from the Chinese Glioma Genome Atlas (CGGA) database, and 669 patients, whose data were collected from The Cancer Genome Atlas database, were enrolled. We further screened the data of a cohort of paired primary and recurrent patients from the CGGA dataset (n = 50). The abundance of immune cells was calculated using the transcriptome data. The association between HIF1A and T-cell exhaustion-related genes and immune cells was investigated.Results: According to the median value of HIF1A expression, gliomas were classified into low-HIF1A-expression and high-HIF1A-expression groups. The expression levels of PDL1 (CD274), FOXO1, and PRDM1 in the high-HIF1A-expression group were significantly higher in both glioblastoma (GBM) and lower-grade glioma. The abundance of exhausted T cells and B cells was significantly higher in the high-HIF1A-expression group, while that of macrophage, monocyte, and natural killer cell was significantly higher in the low-HIF1A-expression group in both GBM and lower-grade glioma. After tumor recurrence, the expression of HIF1A significantly increased, and the correlation between HIF1A expression levels and exhausted T cells and induced regulatory T cells became stronger.Conclusion: In diffuse gliomas, the levels of T-cell exhaustion-associated genes and the abundance of immune cells were elevated under high HIF1A expression. Reversing hypoxia may improve the efficacy of immunotherapy.

scholarly journals Immunological Role And Clinical Prognostic Significance of Risk Marker P2RY6 In Lung Adenocarcinoma

2021 ◽  
Author(s):  
Hong Wu ◽  
Dongxu Hui ◽  
Jiasheng Li ◽  
Lihua Zhang ◽  
Xuebao Xiang
Keyword(s):  
Inflammatory Responses ◽  
Prognostic Significance ◽  
Immune Microenvironment ◽  
Poor Patient ◽  
Different Types ◽  
Risk Scoring ◽  
Patient Prognosis ◽  
Cancer Tissues ◽  
The Relationship

Abstract There is increasing evidence that P2RY6 may be involved in inflammatory responses. However, the role of P2RY6 in a variety of cancers remains unknown. In this study, we comprehensively analyzed P2RY6 expression and its association with different types of malignancies using different multiple databases, and further explored the relationship between P2RY6 expression and prognosis in LUAD, and finally validated it using immunohistochemistry in LUAD. We found that P2RY6 was expressed at significantly higher levels in a variety of cancer tissues, and that poor patient prognosis was strongly associated with high P2RY6 expression. Further risk scoring revealed that P2RY6 is closely associated with the immune microenvironment of LUAD, which would suggest that P2RY6 would be a new target for immunotherapy in LUAD

scholarly journals EGFR mutation: a prognostic factor associated with immune infiltration in lower-grade glioma.

2019 ◽  
Author(s):  
Zhaonian Hao ◽  
Dongsheng Guo
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Cells ◽  
Cd4 T Cells ◽  
Egfr Mutation ◽  
Biological Effects ◽  
Lower Grade ◽  
Immune Infiltration ◽  
Lower Grade Glioma ◽  
Egfr Mutant

Abstract Glioma is one of the most common type of primary central nervous system (CNS) tumors. EGFR mutation, a common alteration occurs in various tumors, is not brought to the forefront in understanding and treating glioma at present. In the present study, we demonstrated an immune infiltration related pattern of EGFR mutation in lower-grade glioma. In silico analyses were performed to investigate EGFR mutation and its biological effects and clinical values. GO and GSEA process were used as enrichment analysis. Infiltration levels of specific types of immune cells were estimated at TIMER database. Clinical data of patients were obtained from TCGA and were employed for survival analyses. Results revealed that EGFR mutation leads to an up-regulation of immune response related pathways and dismal prognosis in lower-grade glioma. Infiltration of CD4+ T cells, neutrophils, macrophages, and dendritic cells were significantly increased in EGFR-mutant cases. Infiltration of specific types of immune cells were correlated with shorter survival time. PD-L1 was elevated in EGFR-mutant cases and correlated with infiltration level of CD4+ T cells, neutrophils and dendritic cells. In conclusion, EGFR mutation indicates increasing infiltration of specific types of immune cells and poor prognosis in lower-grade glioma. Alteration of immune microenvironment since the EGFR mutation might influence the survival of glioma. We also provided a novel evidence and indicator of PD-1 inhibitor application in glioma.

scholarly journals Screening and Identification of Key Biomarkers in Lower Grade Glioma via Bioinformatical Analysis

2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Fangzhou Guo ◽  
Jun Yan ◽  
Guoyuan Ling ◽  
Hainan Chen ◽  
Qianrong Huang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kegg Pathway ◽  
Killer Cell ◽  
Gene Clustering ◽  
Normal Brain ◽  
Lower Grade ◽  
Central Nervous System Tumor ◽  
Tissue Samples ◽  
Lower Grade Glioma ◽  
Core Genes

Lower-grade glioma (LGG) is a common type of central nervous system tumor. Due to its complicated pathogenesis, the choice and timing of adjuvant therapy after tumor treatment are controversial. This study explored and identified potential therapeutic targets for lower-grade. The bioinformatics method was employed to identify potential biomarkers and LGG molecular mechanisms. Firstly, we selected and downloaded GSE15824, GSE50161, and GSE86574 from the GEO database, which included 40 LGG tissue and 28 normal brain tissue samples. GEO and VENN software identified of 206 codifference expressed genes (DEGs). Secondly, we applied the DAVID online software to investigate the DEG biological function and KEGG pathway enrichment, as well as to build the protein interaction visualization network through Cytoscape and STRING website. Then, the MCODE plug is used in the analysis of 22 core genes. Thirdly, the 22 core genes were analyzed with UNCLA software, of which 18 genes were associated with a worse prognosis. Fourthly, GEPIA was used to analyze the 18 selected genes, and 14 genes were found to be a significantly different expression between LGGs and normal brain tumor samples. Fifthly, hierarchical gene clustering was used to examine the 14 important gene expression differences in different histologies, as well as analysis of the KEGG pathway. Five of these genes were shown to be abundant in the natural killer cell-mediated cytokines (NKCC) and phagosome pathways. The five key genes that may be affected by the immune microenvironment play a crucial role in LGG development.

Cancer-associated stroma

2019 ◽  
pp. 303-313
Author(s):  
Wilma Mesker ◽  
Rob Tollenaar
Keyword(s):  
Immune Cells ◽  
Therapy Response ◽  
Tumour Microenvironment ◽  
Process Research ◽  
Cancer Drug ◽  
Cancer Growth ◽  
Tumour Stroma ◽  
Stromal Tissue ◽  
Patient Prognosis

Tumorigenesis is a dynamic process. Research on cancer development and metastases focuses on the tumour ‘host’ interface, and in particular on the role of the stromal tissue. For a few decades now, it has been well established that the tumour-associated stroma affects cancer growth and progression. Fibroblasts of the stroma orchestrate the recruitment of immune cells to promote cancer growth. Moreover, the tumour stroma of each tumour is different in terms of quantity and of cellular composition. The tumour stroma has gained interest in the clinic with regard to patient prognosis and its potential to influence therapy response. Where cancer drug development traditionally focused on targeting the tumour cells, emphasis has now shifted towards the tumour microenvironment for the development of novel therapeutics.

scholarly journals Identification and Verification on Prognostic Index of Lower-Grade Glioma Immune-Related LncRNAs

2020 ◽  
Vol 10 ◽  
Author(s):  
Jing Wen ◽  
Youjun Wang ◽  
Lili Luo ◽  
Lu Peng ◽  
Caixia Chen ◽  
...  
Keyword(s):  
Risk Score ◽  
Immune Cells ◽  
Risk Group ◽  
Prognostic Index ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Lower Grade ◽  
Validation Data ◽  
Lower Grade Glioma ◽  
Immune Group

Previous studies have shown that the prognosis of patients with lower-grade glioma (LGG) is closely related to the infiltration of immune cells and the expression of long non-coding RNAs (lncRNAs). In this paper, we applied single-sample gene set enrichment analysis (ssGSEA) algorithm to evaluate the expression level of immune genes from tumor tissues in The Cancer Genome Atlas (TCGA) database, and divided patients into the high immune group and the low immune group, which were separately analyzed for differential expression. Venn analysis was taken to select 36 immune-related lncRNAs. To construct a prognostic model of LGG based on immune-related lncRNAs, we divided patients into a training set and a verification set at a ratio of 2:1. Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) regression were performed to select 11 immune-related lncRNAs associated with the prognosis of LGG, and based on these selected lncRNAs, the risk scoring model was constructed. Through Kaplan-Meier analysis, the overall survival (OS) of patients in the high-risk group was significantly lower than that of the low-risk group. Then, established a nomogram including age, gender, neoplasm histologic grade, and risk score. Meanwhile, the predictive performance of the model was evaluated by calculating the C-index, drawing the calibration chart, the clinical decision curve as well as the Receiver Operating Characteristic (ROC) curve. Similar results were obtained by utilizing the validation data to verify the above consequences. Based on the TIMER database, the correlation analysis showed that the 11 immune-related lncRNAs risk score of LGG were in connection with the infiltration of the subtypes of immune cells. Subsequently, we performed enrichment analysis, whose results showed that these immune-related lncRNAs played important roles in the progress of LGG. In conclusion, these 11 immune-related lncRNAs have the potential to predict the prognosis of patients with LGG, which may play a key role in the development of LGG.

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