TCGAbiolinks is an R package, which is licensed under the General Public License (GPLv3), and is freely available through the Bioconductor repository (21 (link)). By conforming to the strict guidelines for package submission to Bioconductor, we were able to utilize and incorporate existing R/Bioconductor packages and statistics to assist in identifying differentially altered genomic regions defined by mutation, copy number, expression or DNA methylation; to reproduce previous TCGA marker studies; and to integrate data types both within TCGA and across other data types outside of TCGA. TCGAbiolinks consists of functions that can be grouped into three main levels: Data, Analysis and Visualization. More specifically, the package provides multiple methods for the analysis of individual experimental platforms (e.g. differential expression analysis or identifying differentially methylated regions or copy number alterations) and methods for visualization (e.g. survival plots, volcano plots and starburst plots) to facilitate the development of complete analysis pipelines. In addition, TCGAbiolinks offers in-depth integrative analysis of multiple platforms, such as copy number and expression or expression and DNA methylation, as demonstrated and applied in our recent TCGA study of 1122 gliomas (6 ). These functions can be used independently or in combination to provide the user with fully comprehensible analysis pipelines applied to TCGA data. A schematic overview of the package is presented in Figure 2 . We will describe each of the three main levels (Data, Analysis and Visualization) below, highlighting the importance and utility of each associated function and subfunction. We will then introduce four tumor case studies, which will help clarify the utility of TCGAbiolinks for the reader. We have also compiled an in-depth vignette, which describes every function in detail. Here, we will summarize the main functions.
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Disorders
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Neoplastic Process
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Glioma
Glioma
Gliomas are a diverse group of brain and spinal cord tumors that originate from glial cells, the supportive tissue of the nervous system.
These tumors can vary in aggressiveness, from slow-growing low-grade gliomas to highly malignant glioblastomas.
Gliomas often present with neurological symptoms such as headaches, seizures, and cognitive impairment, and their management typically involves a combination of surgery, radiation, and chemotherapy.
Reserch into more effective treament protocols is critical to improving outcomes for patients with these challenging neoplasms.
These tumors can vary in aggressiveness, from slow-growing low-grade gliomas to highly malignant glioblastomas.
Gliomas often present with neurological symptoms such as headaches, seizures, and cognitive impairment, and their management typically involves a combination of surgery, radiation, and chemotherapy.
Reserch into more effective treament protocols is critical to improving outcomes for patients with these challenging neoplasms.
Most cited protocols related to «Glioma»
Copy Number Polymorphism
DNA Methylation
Genome
Glioma
Mutation
Neoplasms
Glioma
Malignant Neoplasms
Microtubule-Associated Proteins
Neoplasms
TCGA level 3 gene expression levels were obtained from the TCGA Data Portal45 in March 2013. In this study, we used 10 tumour types from four platforms: Affymetrix HT-HG-U133A (one-colour type—that is, one RNA sample is labelled with a fluorophore and hybridized to a microarray), Agilent G4502A (two-colour type—that is, one sample and one reference are labelled with different fluorophores and hybridized together on a same microarray), RNAseq (quantified as Reads Per Kilobase per Million mapped reads)46 (link) and RNAseqV2 (quantified through RNA-seq by Expectation Maximization)47 (link) (Table 1 ). The tumour types selected for our study were among the first tumour types analysed through TCGA and were selected as cancer types studied in TCGA’s Pan-Cancer project. In addition, we used 31 data sets of microarray expression or SNP array copy numbers from Gene Expression Omnibus48 (link) and ArrayExpress49 (link), glioblastoma expression data set from the Repository of Molecular Brain Neoplasia Data50 , cancer cell line expression data set from Cancer Cell Line Encyclopedia (CCLE)51 (link) and a glioma stem-like cell expression data set from researchers at MD Anderson Cancer Center (Supplementary Table S1 ).
Brain Neoplasms
Cell Lines
Gene Expression
Glioblastoma
Glioma
Malignant Neoplasms
Microarray Analysis
Neoplasms
RNA-Seq
Stem Cells
Glioma tissues and corresponding genomic data and patient follow-up information were obtained from Beijing Tiantan Hospital at Capital Medical University, Tianjin Medical University General Hospital, Sanbo Brain Hospital at Capital Medical University, the Second Affiliated Hospital of Harbin Medical University, the First Affiliated Hospital of Nanjing Medical University, and the First Hospital of China Medical University. According to the pathological reassessment of independent neuropathologists, all the subjects were consistently diagnosed with glioma and were then further classified according to the 2007/2016 WHO classification system. The specimens were collected according to protocols approved by the Institutional Review Boards of Beijing Tiantan Hospital (Approval No. IRB KY2013-017-01) and frozen in liquid nitrogen within 5 min of resection.
Brain
Freezing
Genome
Glioma
Neuropathologist
Nitrogen
Patients
Tissues
Cell Lines
Cloning Vectors
Diploid Cell
DNA Methylation
DNA Motifs
Genes
Genome, Human
Glioma
Histocompatibility Testing
Hydatidiform Mole
Induced Pluripotent Stem Cells
Methylation
Microarray Analysis
Multiple Birth Offspring
Pluripotent Stem Cells
RNA, Messenger
RNA-Seq
S-pentachlorobuta-1,3-dien-yl-cysteine
Stem Cells
Transcription, Genetic
Most recents protocols related to «Glioma»
Example 12
The following prophetic example is meant to show how administration of DDFPe can downregulate expression of genes that are over expressed in hypoxic tumor tissue and upregulate expression of genes that are expressed in normoxic tissue (i.e. normalize gene expression). Fischer 344 rats (F344/Ncr; National Cancer Institute, Frederick, MD) were used to generate 9 L glioma tumor models. Pieces of 9 L glioma were tied into the epigastric artery/epigastric vein pair as previously described. The animals received daily IV injections of either 0.45 cc/kg DDFPe or saline until the tumors weighed approximately 1.5-g at which time the animals were euthanized, the tumors removed and flash frozen. Gene expression in the tumors was assayed similarly to that described above. Up-regulated genes seen in the control group included BCL2/adenovirus E1B 19 kDa-interacting protein 3, hemc oxygenase (decycling) 1, activating transcription factor 3, heat shock protein (HSP27), N-myc downstream regulated gene 1, carbonic anhydrase 9 and others. Genes that were downregulated in the control group included Ly6-C antigen, solute carrier family 44 (member2), sterile alpha motif domain containing 9-like, DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 and CD3 molecule delta polypeptide and others. Comparison of gene expression from 9-L glioma tissues from the animals treated with DDFPe showed significant decrease in expression of the genes that were upregulated in the control animals and significant increase in the genes that were downregulated in the control animals; i.e. there was normalization of gene expression in the tumors from animals treated with DDFPe. See, Marotta, Diane, et al. “In vivo profiling of hypoxic gene expression in gliomas using the hypoxia marker EF5 and laser-capture microdissection.” Cancer research 71.3 (2011): 779-789.
Activating Transcription Factor-3
Adenovirus E1B Proteins
Animals
Antigens
aspartyl-aspartic acid
bcl-2 Gene
CA9 protein, human
CD3 Antigens
Epigastric Arteries
Freezing
Gene Expression
Genes
Genes, Neoplasm
Glioma
glutamylalanine
Heat Shock Proteins
HSPB1 protein, human
Hypoxia
Laser Capture Microdissection
Malignant Neoplasms
N-myc Genes
Neoplasms
Oxygen-12
Oxygenases
Pharmacotherapy
Polypeptides
Radiotherapy
Rats, Inbred F344
Saline Solution
Sterile Alpha Motif
Therapeutics
Tissues
Veins
To construct a validated prognostic model, 609 glioma patients were randomly divided into training and testing cohorts. Ultimately, 306 patients were enrolled in the training cohort, and 303 patients were enrolled in the testing cohort. The key characteristics of each cohort are shown in Table 1 . The SRlncRNA signature was derived based on the training cohort, and its potential to predict patient survival was validated utilizing the testing cohort and the whole cohort. We also confirmed the prognostic signature in the TCGA-LGG cohort, the TCGA-GBM cohort and the CGGA cohort (Supplementary Tables S1, S2 ).
The prognostic significance of cellular senescence-related lncRNAs was initially determined using univariate Cox regression. Least absolute shrinkage and selection operator (LASSO) regression was used to integrate the cellular senescence-related lncRNAs with p < 0.05 in univariate analysis. The LASSO results were then included in a multivariate Cox model to generate a risk score. A risk score was calculated using a linear combination of cellular senescence-related lncRNA expression levels multiplied by a regression coefficient (β): risk score = (expression of lncRNAi). Based on the median risk score, the patients were categorized into high-risk and low-risk groups. The log-rank test was used to compare the survival differences between the two groups.
The prognostic significance of cellular senescence-related lncRNAs was initially determined using univariate Cox regression. Least absolute shrinkage and selection operator (LASSO) regression was used to integrate the cellular senescence-related lncRNAs with p < 0.05 in univariate analysis. The LASSO results were then included in a multivariate Cox model to generate a risk score. A risk score was calculated using a linear combination of cellular senescence-related lncRNA expression levels multiplied by a regression coefficient (β): risk score = (expression of lncRNAi). Based on the median risk score, the patients were categorized into high-risk and low-risk groups. The log-rank test was used to compare the survival differences between the two groups.
Cellular Senescence
Glioma
Patients
Population at Risk
RNA, Long Untranslated
The clinical and gene expression data of patients with LGGGBM were obtained from the TCGA database (https://cancergenome.nih.gov/ ) and the CGGA database (http://www.cgga.org.cn/ ). Normal brain RNA sequencing data were obtained from GTEx and utilized as normal control data. In this research, data from 609 glioma samples and 1152 normal brain samples were analyzed. Among them, the data used in the gene expression data were normalized. Next, DEGs were chosen using the R software’s “limma” package with the absolute value of the log2-transformed fold change (FC) > 1 and the adjusted p-value (adj. P) < 0.05 as the cutoff. In addition, the ComBat method was used to reduce batch effects with the R package “sva”.
Brain
Gene Expression
Glioma
Patients
All procedures for this research were approved by the Ethics Committee of Harbin Medical University (Harbin, China). Glioma samples and adjacent normal brain tissue were collected from 24 patients who were resected at Harbin Medical University Cancer Hospital. Patients had not been treated with radiotherapy or chemotherapy before surgery. All tissue samples were pathologically confirmed and immediately frozen in liquid nitrogen for storage until the RNA was extracted. Each patient signed a written informed consent form before the tissue samples were used for research purposes. The clinical characteristics of the 24 glioma patients are shown in Supplementary Table S4 .
The human GBM cell lines (T98G and U251) and the normal human astrocyte cell line (NHA) were obtained from our laboratory (Li et al., 2019a (link)). All cell lines were cultured in Dulbecco’s modified Eagle’s medium (DMEM; SIGMA) supplemented with 10% fetal bovine serum (FBS; PAN SERATECH) at 37°C in a humidified chamber containing 5% CO2. All glioma patients from our hospital were informed and ethical approval for the current research was obtained through the Ethics Committee of Harbin Medical University (KY2021-42).
The human GBM cell lines (T98G and U251) and the normal human astrocyte cell line (NHA) were obtained from our laboratory (Li et al., 2019a (link)). All cell lines were cultured in Dulbecco’s modified Eagle’s medium (DMEM; SIGMA) supplemented with 10% fetal bovine serum (FBS; PAN SERATECH) at 37°C in a humidified chamber containing 5% CO2. All glioma patients from our hospital were informed and ethical approval for the current research was obtained through the Ethics Committee of Harbin Medical University (KY2021-42).
Astrocytes
Brain
Cell Lines
Culture Media
Eagle
Ethics Committees
Freezing
Glioma
Homo sapiens
Inpatient
Malignant Neoplasms
Nitrogen
Operative Surgical Procedures
Patients
Pharmacotherapy
Radiotherapy
Tissues
The Chinese Glioma Genome Atlas (CGGA) database (http://cgga.org.cn/analyse/RNA-data.jsp ) was used to analyse the expression levels of PPP1CA and KIF18A, survival prognosis as well as their correlation. Pearson correlation analysis was performed.
BioGRID (version 4.4;https://thebiogrid.org/ ) and GeneMANIA (https://genemania.org/ ) databases were used to analyse the interaction between KIF18A and PPP1CA.
BioGRID (version 4.4;
Chinese
Genome
Glioma
KIF18A protein, human
PPP1CA protein, human
Prognosis
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Fetal Bovine Serum (FBS) is a cell culture supplement derived from the blood of bovine fetuses. FBS provides a source of proteins, growth factors, and other components that support the growth and maintenance of various cell types in in vitro cell culture applications.
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DMEM (Dulbecco's Modified Eagle's Medium) is a cell culture medium formulated to support the growth and maintenance of a variety of cell types, including mammalian cells. It provides essential nutrients, amino acids, vitamins, and other components necessary for cell proliferation and survival in an in vitro environment.
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Penicillin/streptomycin is a commonly used antibiotic solution for cell culture applications. It contains a combination of penicillin and streptomycin, which are broad-spectrum antibiotics that inhibit the growth of both Gram-positive and Gram-negative bacteria.
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Lipofectamine 2000 is a cationic lipid-based transfection reagent designed for efficient and reliable delivery of nucleic acids, such as plasmid DNA and small interfering RNA (siRNA), into a wide range of eukaryotic cell types. It facilitates the formation of complexes between the nucleic acid and the lipid components, which can then be introduced into cells to enable gene expression or gene silencing studies.
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Streptomycin is a broad-spectrum antibiotic used in laboratory settings. It functions as a protein synthesis inhibitor, targeting the 30S subunit of bacterial ribosomes, which plays a crucial role in the translation of genetic information into proteins. Streptomycin is commonly used in microbiological research and applications that require selective inhibition of bacterial growth.
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Penicillin is a type of antibiotic used in laboratory settings. It is a broad-spectrum antimicrobial agent effective against a variety of bacteria. Penicillin functions by disrupting the bacterial cell wall, leading to cell death.
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U87MG is a human glioblastoma cell line derived from a malignant brain tumor. It is a well-established model system used in cancer research and drug discovery studies.
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The LN229 is a cell line derived from human glioblastoma. It is a commonly used in vitro model for the study of glioblastoma, a type of brain cancer. The LN229 cell line is available for purchase from the American Type Culture Collection (ATCC) for research purposes.
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More about "Glioma"
Gliomas are a diverse group of brain and spinal cord tumors that originate from glial cells, the supportive tissue of the nervous system.
These neoplasms, also known as glioblastomas, astrocytomas, or oligodendrogliomas, can vary greatly in their aggressiveness, from slow-growing low-grade gliomas to highly malignant glioblastoma multiforme (GBM).
Patients with gliomas often present with neurological symptoms such as headaches, seizures, and cognitive impairment.
The management of these challenging tumors typically involves a combination of surgical resection, radiation therapy, and chemotherapy, with agents like temozolomide, carmustine, or bevacizumab.
Researchers are constantly seeking to improve treatment protocols and outcomes for patients with gliomas.
In the laboratory, glioma cell lines like U87MG and LN229 are commonly used to study these tumors.
Researchers may culture the cells in media like DMEM, supplemented with FBS, penicillin/streptomycin, and other growth factors like EGF.
Techniques such as lipofectamine-mediated transfection and TRIzol-based RNA extraction are often employed to investigate the molecular mechanisms underlying glioma development and progression.
Advancing our understanding of gliomas and developing more effective treatment strategies is crucial for improving the prognosis and quality of life for patients battling these devastating brain and spinal cord cancers.
Continued research, including the optimization of experimental protocols, is essential to making progress in this critical area of neuro-oncology.
These neoplasms, also known as glioblastomas, astrocytomas, or oligodendrogliomas, can vary greatly in their aggressiveness, from slow-growing low-grade gliomas to highly malignant glioblastoma multiforme (GBM).
Patients with gliomas often present with neurological symptoms such as headaches, seizures, and cognitive impairment.
The management of these challenging tumors typically involves a combination of surgical resection, radiation therapy, and chemotherapy, with agents like temozolomide, carmustine, or bevacizumab.
Researchers are constantly seeking to improve treatment protocols and outcomes for patients with gliomas.
In the laboratory, glioma cell lines like U87MG and LN229 are commonly used to study these tumors.
Researchers may culture the cells in media like DMEM, supplemented with FBS, penicillin/streptomycin, and other growth factors like EGF.
Techniques such as lipofectamine-mediated transfection and TRIzol-based RNA extraction are often employed to investigate the molecular mechanisms underlying glioma development and progression.
Advancing our understanding of gliomas and developing more effective treatment strategies is crucial for improving the prognosis and quality of life for patients battling these devastating brain and spinal cord cancers.
Continued research, including the optimization of experimental protocols, is essential to making progress in this critical area of neuro-oncology.