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 |
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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. |
doi_str_mv | 10.1007/s00432-022-04431-1 |
format | Article |
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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.</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 & 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. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. 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.
Conclusion
The prognostic RNA methylation-related alternative splicing signature constructed could constitute a promising prognostic biomarker, which could serve to optimize treatment regimens.</description><subject>Algorithms</subject><subject>Alternative Splicing</subject><subject>Cancer Research</subject><subject>Chemotherapy</subject><subject>DNA methylation</subject><subject>Glioma</subject><subject>Glioma - genetics</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immune checkpoint</subject><subject>Immunosuppressive agents</subject><subject>Immunotherapy</subject><subject>Internal Medicine</subject><subject>Life span</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methylation</subject><subject>Microenvironments</subject><subject>Nomograms</subject><subject>Oncology</subject><subject>Prognosis</subject><subject>Ribonucleic acid</subject><subject>Risk groups</subject><subject>RNA</subject><subject>Survival analysis</subject><subject>Tumor Microenvironment - genetics</subject><issn>0171-5216</issn><issn>1432-1335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc1u1TAQhS0EoreFF2CBLLFhE_DEcewsq4qfShWVqrKOHHsSXDlxsJOL-iy8LL43pUgsurA8c_zNjDWHkDfAPgBj8mNirOJlwcp8qopDAc_IDg4ScC6ekx0DCYUooT4hpyndsZwLWb4kJ7wWpVIcduT3pcVpcb0zenFhonqydK-9s1saenrz7ZyOuPy490epiJgDtFT7BeOUtT3SNHtn3DTQAaecuSHra0Tah0h9-FUMUVukg3dh1HQJdI5onVloWuPe5XHHsW4c11ztc5yMnjG9Ii967RO-frjPyPfPn24vvhZX118uL86vCsPLein6yqim4bqTtre87CplbGOgQp63wLiVRgvVKNVVle44V6rpoO5qbcEKhhL5GXm_9Z1j-LliWtrRJYM-_wTDmtpSCiEUA2gy-u4_9C6seQv-QEkA2TSSZ6rcKBNDShH7do5u1PG-BdYerGs369psXXu0roVc9Pah9dqNaB9L_nqVAb4BKT9NA8Z_s59o-wf17KcM</recordid><startdate>2023</startdate><enddate>2023</enddate><creator>Ma, Chenggong</creator><creator>Bao, Yunong</creator><creator>Xu, Jiazhe</creator><creator>Xiao, Bo</creator><creator>Li, Hui</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4759-1779</orcidid></search><sort><creationdate>2023</creationdate><title>Identification and validation of RNA methylation-related alternative splicing gene signature for low-grade glioma to predict survival and immune landscapes</title><author>Ma, Chenggong ; Bao, Yunong ; Xu, Jiazhe ; Xiao, Bo ; Li, Hui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-f4c8993ab7dfd32b48cd9c14e333503d7ca58988b44ab33889b16b6ad1d50e7e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Algorithms</topic><topic>Alternative Splicing</topic><topic>Cancer Research</topic><topic>Chemotherapy</topic><topic>DNA methylation</topic><topic>Glioma</topic><topic>Glioma - genetics</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immune checkpoint</topic><topic>Immunosuppressive agents</topic><topic>Immunotherapy</topic><topic>Internal Medicine</topic><topic>Life span</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Methylation</topic><topic>Microenvironments</topic><topic>Nomograms</topic><topic>Oncology</topic><topic>Prognosis</topic><topic>Ribonucleic acid</topic><topic>Risk groups</topic><topic>RNA</topic><topic>Survival analysis</topic><topic>Tumor Microenvironment - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Chenggong</creatorcontrib><creatorcontrib>Bao, Yunong</creatorcontrib><creatorcontrib>Xu, Jiazhe</creatorcontrib><creatorcontrib>Xiao, Bo</creatorcontrib><creatorcontrib>Li, Hui</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Proquest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cancer research and clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Chenggong</au><au>Bao, Yunong</au><au>Xu, Jiazhe</au><au>Xiao, Bo</au><au>Li, Hui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and validation of RNA methylation-related alternative splicing gene signature for low-grade glioma to predict survival and immune landscapes</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><stitle>J Cancer Res Clin Oncol</stitle><addtitle>J Cancer Res Clin Oncol</addtitle><date>2023</date><risdate>2023</risdate><volume>149</volume><issue>1</issue><spage>47</spage><epage>62</epage><pages>47-62</pages><issn>0171-5216</issn><eissn>1432-1335</eissn><abstract>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.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>36528831</pmid><doi>10.1007/s00432-022-04431-1</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-4759-1779</orcidid></addata></record> |
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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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