Pan-cancer analysis of clinical relevance of alternative splicing events in 31 human cancers
Alternative splicing represents a critical posttranscriptional regulation of gene expression, which contributes to the protein complexity and mRNA processing. Defects of alternative splicing including genetic alteration and/or altered expression of both pre-mRNA and trans-acting factors give rise to...
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| Veröffentlicht in: | Oncogene 2019-10, Vol.38 (40), p.6678-6695 |
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| container_title | Oncogene |
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| creator | Zhang, Yangjun Yan, Libin Zeng, Jin Zhou, Hui Liu, Haoran Yu, Gan Yao, Weimin Chen, Ke Ye, Zhangqun Xu, Hua |
| description | Alternative splicing represents a critical posttranscriptional regulation of gene expression, which contributes to the protein complexity and mRNA processing. Defects of alternative splicing including genetic alteration and/or altered expression of both pre-mRNA and trans-acting factors give rise to many cancers. By integrally analyzing clinical data and splicing data from TCGA and SpliceSeq databases, a number of splicing events were found clinically relevant in tumor samples. Alternative splicing of KLK2 (KLK2_51239) was found as a potential inducement of nonsense-mediated mRNA decay and associated with poor survival in prostate cancer. Consensus K-means clustering analysis indicated that alternative splicing events could be potentially used for molecular subtype classification of cancers. By random forest survival algorithm, prognostic prediction signatures with well performances were constructed for 31 cancers by using survival-associated alternative splicing events. Furthermore, an online tool for visualization of Kaplan–Meier plots of splicing events in 31 cancers was explored. Briefly, alternative splicing was found of significant clinical relevance with cancers. |
| doi_str_mv | 10.1038/s41388-019-0910-7 |
| format | Article |
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Defects of alternative splicing including genetic alteration and/or altered expression of both pre-mRNA and trans-acting factors give rise to many cancers. By integrally analyzing clinical data and splicing data from TCGA and SpliceSeq databases, a number of splicing events were found clinically relevant in tumor samples. Alternative splicing of KLK2 (KLK2_51239) was found as a potential inducement of nonsense-mediated mRNA decay and associated with poor survival in prostate cancer. Consensus K-means clustering analysis indicated that alternative splicing events could be potentially used for molecular subtype classification of cancers. By random forest survival algorithm, prognostic prediction signatures with well performances were constructed for 31 cancers by using survival-associated alternative splicing events. Furthermore, an online tool for visualization of Kaplan–Meier plots of splicing events in 31 cancers was explored. Briefly, alternative splicing was found of significant clinical relevance with cancers.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-019-0910-7</identifier><identifier>PMID: 31391553</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38 ; 38/91 ; 45 ; 631/208/1792 ; 631/67/68 ; 692/53/2422 ; Alternative Splicing ; Apoptosis ; Care and treatment ; Cell Biology ; Gene expression ; Genetic aspects ; Human Genetics ; Humans ; Internal Medicine ; Kaplan-Meier Estimate ; Medicine ; Medicine & Public Health ; Messenger RNA ; mRNA processing ; mRNA turnover ; Neoplasms - genetics ; Neoplasms - pathology ; Nonsense-mediated mRNA decay ; Oncology ; Post-transcription ; Prognosis ; Prostate cancer ; Survival</subject><ispartof>Oncogene, 2019-10, Vol.38 (40), p.6678-6695</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2019</rights><rights>COPYRIGHT 2019 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-9660db96005234c1286cf505114b8541e8972dfafca5b5a482181da987fd37753</citedby><cites>FETCH-LOGICAL-c505t-9660db96005234c1286cf505114b8541e8972dfafca5b5a482181da987fd37753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41388-019-0910-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41388-019-0910-7$$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/31391553$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yangjun</creatorcontrib><creatorcontrib>Yan, Libin</creatorcontrib><creatorcontrib>Zeng, Jin</creatorcontrib><creatorcontrib>Zhou, Hui</creatorcontrib><creatorcontrib>Liu, Haoran</creatorcontrib><creatorcontrib>Yu, Gan</creatorcontrib><creatorcontrib>Yao, Weimin</creatorcontrib><creatorcontrib>Chen, Ke</creatorcontrib><creatorcontrib>Ye, Zhangqun</creatorcontrib><creatorcontrib>Xu, Hua</creatorcontrib><title>Pan-cancer analysis of clinical relevance of alternative splicing events in 31 human cancers</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Alternative splicing represents a critical posttranscriptional regulation of gene expression, which contributes to the protein complexity and mRNA processing. Defects of alternative splicing including genetic alteration and/or altered expression of both pre-mRNA and trans-acting factors give rise to many cancers. By integrally analyzing clinical data and splicing data from TCGA and SpliceSeq databases, a number of splicing events were found clinically relevant in tumor samples. Alternative splicing of KLK2 (KLK2_51239) was found as a potential inducement of nonsense-mediated mRNA decay and associated with poor survival in prostate cancer. Consensus K-means clustering analysis indicated that alternative splicing events could be potentially used for molecular subtype classification of cancers. By random forest survival algorithm, prognostic prediction signatures with well performances were constructed for 31 cancers by using survival-associated alternative splicing events. Furthermore, an online tool for visualization of Kaplan–Meier plots of splicing events in 31 cancers was explored. Briefly, alternative splicing was found of significant clinical relevance with cancers.</description><subject>38</subject><subject>38/91</subject><subject>45</subject><subject>631/208/1792</subject><subject>631/67/68</subject><subject>692/53/2422</subject><subject>Alternative Splicing</subject><subject>Apoptosis</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Kaplan-Meier Estimate</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Messenger RNA</subject><subject>mRNA processing</subject><subject>mRNA turnover</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - pathology</subject><subject>Nonsense-mediated mRNA decay</subject><subject>Oncology</subject><subject>Post-transcription</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>Survival</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</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>eNp1kc1rFTEUxYMo9ln9A9xIwI2b1JuvSbIspX5AQRe6E0JeJvNMyWSeycyD_vdmmGpRlCwC9_zO4V4OQi8pXFDg-m0VlGtNgBoChgJRj9COCtURKY14jHZgJBDDODtDz2q9BQBlgD1FZ5xyQ6XkO_Tts8vEu-xDwS67dFdjxdOAfYo5epdwCSmcVn2dujSHkt0cTwHXY4o-5gMOp5DnimPGnOLvy-gy3gLrc_RkcKmGF_f_Ofr67vrL1Qdy8-n9x6vLG-IlyJmYroN-bzoAybjwlOnOD02hVOy1FDRoo1g_uME7uZdOaEY17Z3Raui5UpKfozdb7rFMP5ZQZzvG6kNKLodpqZYxBUCBCdHQ13-ht9PSTkqN4g3qQEh4oA4uBRvzMM3F-TXUXnZApdJa8UZd_INqrw9j9FMOQ2zzPwx0M_gy1VrCYI8ljq7cWQp2bdRujdrWqF0btap5Xt0vvOzH0P92_KqwAWwDapPyIZSHi_6f-hMkoqf0</recordid><startdate>20191003</startdate><enddate>20191003</enddate><creator>Zhang, Yangjun</creator><creator>Yan, Libin</creator><creator>Zeng, Jin</creator><creator>Zhou, Hui</creator><creator>Liu, Haoran</creator><creator>Yu, Gan</creator><creator>Yao, Weimin</creator><creator>Chen, Ke</creator><creator>Ye, Zhangqun</creator><creator>Xu, Hua</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20191003</creationdate><title>Pan-cancer analysis of clinical relevance of alternative splicing events in 31 human cancers</title><author>Zhang, Yangjun ; Yan, Libin ; Zeng, Jin ; Zhou, Hui ; Liu, Haoran ; Yu, Gan ; Yao, Weimin ; Chen, Ke ; Ye, Zhangqun ; Xu, Hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-9660db96005234c1286cf505114b8541e8972dfafca5b5a482181da987fd37753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>38</topic><topic>38/91</topic><topic>45</topic><topic>631/208/1792</topic><topic>631/67/68</topic><topic>692/53/2422</topic><topic>Alternative Splicing</topic><topic>Apoptosis</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Kaplan-Meier Estimate</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Messenger RNA</topic><topic>mRNA processing</topic><topic>mRNA turnover</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - pathology</topic><topic>Nonsense-mediated mRNA decay</topic><topic>Oncology</topic><topic>Post-transcription</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>Survival</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yangjun</creatorcontrib><creatorcontrib>Yan, Libin</creatorcontrib><creatorcontrib>Zeng, Jin</creatorcontrib><creatorcontrib>Zhou, Hui</creatorcontrib><creatorcontrib>Liu, Haoran</creatorcontrib><creatorcontrib>Yu, Gan</creatorcontrib><creatorcontrib>Yao, Weimin</creatorcontrib><creatorcontrib>Chen, Ke</creatorcontrib><creatorcontrib>Ye, Zhangqun</creatorcontrib><creatorcontrib>Xu, Hua</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>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yangjun</au><au>Yan, Libin</au><au>Zeng, Jin</au><au>Zhou, Hui</au><au>Liu, Haoran</au><au>Yu, Gan</au><au>Yao, Weimin</au><au>Chen, Ke</au><au>Ye, Zhangqun</au><au>Xu, Hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pan-cancer analysis of clinical relevance of alternative splicing events in 31 human cancers</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2019-10-03</date><risdate>2019</risdate><volume>38</volume><issue>40</issue><spage>6678</spage><epage>6695</epage><pages>6678-6695</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Alternative splicing represents a critical posttranscriptional regulation of gene expression, which contributes to the protein complexity and mRNA processing. Defects of alternative splicing including genetic alteration and/or altered expression of both pre-mRNA and trans-acting factors give rise to many cancers. By integrally analyzing clinical data and splicing data from TCGA and SpliceSeq databases, a number of splicing events were found clinically relevant in tumor samples. Alternative splicing of KLK2 (KLK2_51239) was found as a potential inducement of nonsense-mediated mRNA decay and associated with poor survival in prostate cancer. Consensus K-means clustering analysis indicated that alternative splicing events could be potentially used for molecular subtype classification of cancers. By random forest survival algorithm, prognostic prediction signatures with well performances were constructed for 31 cancers by using survival-associated alternative splicing events. Furthermore, an online tool for visualization of Kaplan–Meier plots of splicing events in 31 cancers was explored. Briefly, alternative splicing was found of significant clinical relevance with cancers.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31391553</pmid><doi>10.1038/s41388-019-0910-7</doi><tpages>18</tpages></addata></record> |
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| ispartof | Oncogene, 2019-10, Vol.38 (40), p.6678-6695 |
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| subjects | 38 38/91 45 631/208/1792 631/67/68 692/53/2422 Alternative Splicing Apoptosis Care and treatment Cell Biology Gene expression Genetic aspects Human Genetics Humans Internal Medicine Kaplan-Meier Estimate Medicine Medicine & Public Health Messenger RNA mRNA processing mRNA turnover Neoplasms - genetics Neoplasms - pathology Nonsense-mediated mRNA decay Oncology Post-transcription Prognosis Prostate cancer Survival |
| title | Pan-cancer analysis of clinical relevance of alternative splicing events in 31 human cancers |
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