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      Identification of cuproptosis‐related lncRNAs for prognosis and immunotherapy in glioma

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          Abstract

          Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis‐related genes have prognostic predictive value has not been clarified. In this study, uni‐/multi‐variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis‐related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high‐ and low‐risk groups. Either for grade 2–3 or for grade 4, glioma patients with high‐risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high‐risk group was functionally associated with immune responses and cancer‐related pathways. The high‐risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high‐risk group were significantly higher than those in the low‐risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T‐cell co‐stimulation pathways. In conclusion, we established a risk model based on cuproptosis‐related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno‐microenvironment status of glioma.

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          Most cited references41

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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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            Maftools: efficient and comprehensive analysis of somatic variants in cancer

            Numerous large-scale genomic studies of matched tumor-normal samples have established the somatic landscapes of most cancer types. However, the downstream analysis of data from somatic mutations entails a number of computational and statistical approaches, requiring usage of independent software and numerous tools. Here, we describe an R Bioconductor package, Maftools, which offers a multitude of analysis and visualization modules that are commonly used in cancer genomic studies, including driver gene identification, pathway, signature, enrichment, and association analyses. Maftools only requires somatic variants in Mutation Annotation Format (MAF) and is independent of larger alignment files. With the implementation of well-established statistical and computational methods, Maftools facilitates data-driven research and comparative analysis to discover novel results from publicly available data sets. In the present study, using three of the well-annotated cohorts from The Cancer Genome Atlas (TCGA), we describe the application of Maftools to reproduce known results. More importantly, we show that Maftools can also be used to uncover novel findings through integrative analysis.
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              Tumor mutational load predicts survival after immunotherapy across multiple cancer types

              Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in select cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI.To examine this association more broadly, we analyzed the clinical and genomic data of 1662 advanced cancer patients treated with ICI, and 5371 non-ICI treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Among all patients, higher somatic TMB (highest 20% in each histology) was associated with better OS (HR 0.52; p=1.6 ×10 −6 ). For most cancer histologies, an association between higher TMB and improved survival was observed. The TMB cutpoints associated with improved survival varied markedly between cancer types. These data indicate that TMB is associated with improved survival in patients receiving ICI across a wide variety of cancer types, but that there may not be one universal definition of high TMB.
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                Author and article information

                Contributors
                cjj@jlu.edu.cn
                wang_ziqian@outlook.com
                Journal
                J Cell Mol Med
                J Cell Mol Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                01 November 2022
                December 2022
                : 26
                : 23 ( doiID: 10.1111/jcmm.v26.23 )
                : 5820-5831
                Affiliations
                [ 1 ] Department of Neurology China‐Japan Union Hospital of Jilin University Changchun China
                [ 2 ] Department of Neurosurgical Oncology The First Hospital of Jilin University Changchun China
                Author notes
                [*] [* ] Correspondence

                Jiajun Chen, Department of Neurology, China‐Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.

                Email: cjj@ 123456jlu.edu.cn

                Ziqian Wang, Department of Neurosurgical Oncology, The First Hospital of Jilin University, Changchun, Jilin 130021, China.

                Email: wang_ziqian@ 123456outlook.com

                Author information
                https://orcid.org/0000-0002-1232-6687
                Article
                JCMM17603 JCMM-06-2022-083.R1
                10.1111/jcmm.17603
                9716210
                36317420
                63b8c3cd-174d-4245-b583-2ba0849159c3
                © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 September 2022
                : 20 June 2022
                : 05 October 2022
                Page count
                Figures: 8, Tables: 0, Pages: 12, Words: 5248
                Funding
                Funded by: Norman Bethune Program of Jilin University
                Award ID: 2022B28
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 82203647
                Funded by: Jilin University , doi 10.13039/501100004032;
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                December 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.1 mode:remove_FC converted:02.12.2022

                Molecular medicine
                cuproptosis,glioma,lncrna,prognosis,risk score
                Molecular medicine
                cuproptosis, glioma, lncrna, prognosis, risk score

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