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      Identification of hub genes and biological pathways in glioma via integrated bioinformatics analysis

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          Abstract

          Objective

          Glioma is the most common intracranial primary malignancy, but its pathogenesis remains unclear.

          Methods

          We integrated four eligible glioma microarray datasets from the gene expression omnibus database using the robust rank aggregation method to identify a group of significantly differently expressed genes (DEGs) between glioma and normal samples. We used these DEGs to explore key genes closely associated with glioma survival through weighted gene co-expression network analysis. We then constructed validations of prognosis and survival analyses for the key genes via multiple databases. We also explored their potential biological functions using gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA).

          Results

          We selected DLGAP5, CDCA8, NCAPH, and CCNB2, as four genes that were abnormally up-regulated in glioma samples, for verification. They showed high levels of isocitrate dehydrogenase gene mutation and tumor grades, as well as good prognostic and diagnostic value for glioma. Their methylation levels were generally lower in glioma samples. GSEA and GSVA analyses suggested the genes were closely involved with glioma proliferation.

          Conclusion

          These findings provide new insights into the pathogenesis of glioma. The hub genes have the potential to be used as diagnostic and therapeutic markers.

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          Most cited references37

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          limma powers differential expression analyses for RNA-sequencing and microarray studies

          limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
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            TIMER2.0 for analysis of tumor-infiltrating immune cells

            Abstract Tumor progression and the efficacy of immunotherapy are strongly influenced by the composition and abundance of immune cells in the tumor microenvironment. Due to the limitations of direct measurement methods, computational algorithms are often used to infer immune cell composition from bulk tumor transcriptome profiles. These estimated tumor immune infiltrate populations have been associated with genomic and transcriptomic changes in the tumors, providing insight into tumor–immune interactions. However, such investigations on large-scale public data remain challenging. To lower the barriers for the analysis of complex tumor–immune interactions, we significantly improved our previous web platform TIMER. Instead of just using one algorithm, TIMER2.0 (http://timer.cistrome.org/) provides more robust estimation of immune infiltration levels for The Cancer Genome Atlas (TCGA) or user-provided tumor profiles using six state-of-the-art algorithms. TIMER2.0 provides four modules for investigating the associations between immune infiltrates and genetic or clinical features, and four modules for exploring cancer-related associations in the TCGA cohorts. Each module can generate a functional heatmap table, enabling the user to easily identify significant associations in multiple cancer types simultaneously. Overall, the TIMER2.0 web server provides comprehensive analysis and visualization functions of tumor infiltrating immune cells.
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              Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.

              The prediction of clinical behavior, response to therapy, and outcome of infiltrative glioma is challenging. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). We tested the hypothesis that within groups based on these features, tumors would have similar clinical variables, acquired somatic alterations, and germline variants.
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                Author and article information

                Journal
                J Int Med Res
                J Int Med Res
                IMR
                spimr
                The Journal of International Medical Research
                SAGE Publications (Sage UK: London, England )
                0300-0605
                1473-2300
                June 2022
                8 June 2022
                : 50
                : 6
                : 03000605221103976
                Affiliations
                [1-03000605221103976]Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
                Author notes
                [*]

                These authors contributed equally to this work.

                [*]Yongxuan Zhao, No. 287 Changhuai Road, Bengbu City, Anhui Province, Bengbu 233000, China. Email: bbneudoc@ 123456163.com
                Author information
                https://orcid.org/0000-0001-9976-0728
                Article
                10.1177_03000605221103976
                10.1177/03000605221103976
                9189557
                35676807
                bc6a011f-39fd-4e3e-9f4c-4ae40d20b7b3
                © The Author(s) 2022

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 17 April 2022
                : 10 May 2022
                Funding
                Funded by: Natural Science Key Project of Bengbu Medical College;
                Award ID: No. 2020byzd065
                Categories
                Pre-Clinical Research Report
                Custom metadata
                ts2

                glioma,hub genes,robust rank aggregation,bioinformatics,biomarker,differential expression

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