Identification and validation of RNA methylation-related alternative splicing gene signature for low-grade glioma to predict survival and immune landscapes

Background Low-grade glioma (LGG) is a crucial pathological type of glioma. The present study aimed to explore multiple RNA methylation regulator-related AS events and investigate their prognostic values in LGG. Methods The prognostic model for low-grade glioma was established using the LASSO regres...

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Veröffentlicht in:Journal of cancer research and clinical oncology 2023, Vol.149 (1), p.47-62
Hauptverfasser: Ma, Chenggong, Bao, Yunong, Xu, Jiazhe, Xiao, Bo, Li, Hui
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creator Ma, Chenggong
Bao, Yunong
Xu, Jiazhe
Xiao, Bo
Li, Hui
description Background Low-grade glioma (LGG) is a crucial pathological type of glioma. The present study aimed to explore multiple RNA methylation regulator-related AS events and investigate their prognostic values in LGG. Methods The prognostic model for low-grade glioma was established using the LASSO regression analysis. To validate prognostic value, we performed Kaplan–Maier survival analysis, ROC curves and nomograms. The ESTIMATE algorithm, the CIBERSORT algorithm and the ssGSEA algorithm were utilized to explore the role of the immune microenvironment in LGG. Subsequently, we then used GO, KEGG and GSEA enrichment analysis to explore the functional roles of these genes. In addition, we employed the GDSC database to screen potential chemotherapeutic agents. Results Eight RNA methylation related AS events were involved in construct a survival and prognosis model, which had good ability of independent prediction for patients with LGG. Patients in the high-risk group had shorter life expectancy and higher mortality, while patients in the low-risk group had a better prognosis. We constructed a nomogram which showed an excellent predictive performance for individual OS. The risk score exhibited a close correlation with some immune cells and expression of immune checkpoints. Patients in high-risk group were characterized by immunosuppressive microenvironment and poor response to immunotherapy, and were sensitive to more chemotherapeutic drugs. Pathway and functional enrichment analyses further confirmed that significant differences existed in immune landscape between the two subgroups. Conclusion The prognostic RNA methylation-related alternative splicing signature constructed could constitute a promising prognostic biomarker, which could serve to optimize treatment regimens.
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The present study aimed to explore multiple RNA methylation regulator-related AS events and investigate their prognostic values in LGG. Methods The prognostic model for low-grade glioma was established using the LASSO regression analysis. To validate prognostic value, we performed Kaplan–Maier survival analysis, ROC curves and nomograms. The ESTIMATE algorithm, the CIBERSORT algorithm and the ssGSEA algorithm were utilized to explore the role of the immune microenvironment in LGG. Subsequently, we then used GO, KEGG and GSEA enrichment analysis to explore the functional roles of these genes. In addition, we employed the GDSC database to screen potential chemotherapeutic agents. Results Eight RNA methylation related AS events were involved in construct a survival and prognosis model, which had good ability of independent prediction for patients with LGG. Patients in the high-risk group had shorter life expectancy and higher mortality, while patients in the low-risk group had a better prognosis. We constructed a nomogram which showed an excellent predictive performance for individual OS. The risk score exhibited a close correlation with some immune cells and expression of immune checkpoints. Patients in high-risk group were characterized by immunosuppressive microenvironment and poor response to immunotherapy, and were sensitive to more chemotherapeutic drugs. Pathway and functional enrichment analyses further confirmed that significant differences existed in immune landscape between the two subgroups. Conclusion The prognostic RNA methylation-related alternative splicing signature constructed could constitute a promising prognostic biomarker, which could serve to optimize treatment regimens.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-022-04431-1</identifier><identifier>PMID: 36528831</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Algorithms ; Alternative Splicing ; Cancer Research ; Chemotherapy ; DNA methylation ; Glioma ; Glioma - genetics ; Hematology ; Humans ; Immune checkpoint ; Immunosuppressive agents ; Immunotherapy ; Internal Medicine ; Life span ; Medical prognosis ; Medicine ; Medicine &amp; Public Health ; Methylation ; Microenvironments ; Nomograms ; Oncology ; Prognosis ; Ribonucleic acid ; Risk groups ; RNA ; Survival analysis ; Tumor Microenvironment - genetics</subject><ispartof>Journal of cancer research and clinical oncology, 2023, Vol.149 (1), p.47-62</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022. 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The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-f4c8993ab7dfd32b48cd9c14e333503d7ca58988b44ab33889b16b6ad1d50e7e3</cites><orcidid>0000-0003-4759-1779</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00432-022-04431-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00432-022-04431-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36528831$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Chenggong</creatorcontrib><creatorcontrib>Bao, Yunong</creatorcontrib><creatorcontrib>Xu, Jiazhe</creatorcontrib><creatorcontrib>Xiao, Bo</creatorcontrib><creatorcontrib>Li, Hui</creatorcontrib><title>Identification and validation of RNA methylation-related alternative splicing gene signature for low-grade glioma to predict survival and immune landscapes</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><addtitle>J Cancer Res Clin Oncol</addtitle><description>Background Low-grade glioma (LGG) is a crucial pathological type of glioma. The present study aimed to explore multiple RNA methylation regulator-related AS events and investigate their prognostic values in LGG. Methods The prognostic model for low-grade glioma was established using the LASSO regression analysis. To validate prognostic value, we performed Kaplan–Maier survival analysis, ROC curves and nomograms. The ESTIMATE algorithm, the CIBERSORT algorithm and the ssGSEA algorithm were utilized to explore the role of the immune microenvironment in LGG. Subsequently, we then used GO, KEGG and GSEA enrichment analysis to explore the functional roles of these genes. In addition, we employed the GDSC database to screen potential chemotherapeutic agents. Results Eight RNA methylation related AS events were involved in construct a survival and prognosis model, which had good ability of independent prediction for patients with LGG. Patients in the high-risk group had shorter life expectancy and higher mortality, while patients in the low-risk group had a better prognosis. We constructed a nomogram which showed an excellent predictive performance for individual OS. The risk score exhibited a close correlation with some immune cells and expression of immune checkpoints. Patients in high-risk group were characterized by immunosuppressive microenvironment and poor response to immunotherapy, and were sensitive to more chemotherapeutic drugs. Pathway and functional enrichment analyses further confirmed that significant differences existed in immune landscape between the two subgroups. 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The present study aimed to explore multiple RNA methylation regulator-related AS events and investigate their prognostic values in LGG. Methods The prognostic model for low-grade glioma was established using the LASSO regression analysis. To validate prognostic value, we performed Kaplan–Maier survival analysis, ROC curves and nomograms. The ESTIMATE algorithm, the CIBERSORT algorithm and the ssGSEA algorithm were utilized to explore the role of the immune microenvironment in LGG. Subsequently, we then used GO, KEGG and GSEA enrichment analysis to explore the functional roles of these genes. In addition, we employed the GDSC database to screen potential chemotherapeutic agents. Results Eight RNA methylation related AS events were involved in construct a survival and prognosis model, which had good ability of independent prediction for patients with LGG. Patients in the high-risk group had shorter life expectancy and higher mortality, while patients in the low-risk group had a better prognosis. We constructed a nomogram which showed an excellent predictive performance for individual OS. The risk score exhibited a close correlation with some immune cells and expression of immune checkpoints. Patients in high-risk group were characterized by immunosuppressive microenvironment and poor response to immunotherapy, and were sensitive to more chemotherapeutic drugs. Pathway and functional enrichment analyses further confirmed that significant differences existed in immune landscape between the two subgroups. 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subjects Algorithms
Alternative Splicing
Cancer Research
Chemotherapy
DNA methylation
Glioma
Glioma - genetics
Hematology
Humans
Immune checkpoint
Immunosuppressive agents
Immunotherapy
Internal Medicine
Life span
Medical prognosis
Medicine
Medicine & Public Health
Methylation
Microenvironments
Nomograms
Oncology
Prognosis
Ribonucleic acid
Risk groups
RNA
Survival analysis
Tumor Microenvironment - genetics
title Identification and validation of RNA methylation-related alternative splicing gene signature for low-grade glioma to predict survival and immune landscapes
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