5-hydroxymethylcytosine loss is associated with poor prognosis for patients with WHO grade II diffuse astrocytomas
Currently, the reliable prognostic biomarkers for WHO grade II diffuse astrocytomas (DA) are still limited. We investigated the relations between the level of 5-Hydroxymethylcytosine (5hmC), an oxidated production of 5-methylcytosine (5mC) by the ten eleven translocated (TET) enzymes, and clinicopat...
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creator | Zhang, Feng Liu, Yifan Zhang, Zhiwen Li, Jie Wan, Yi Zhang, Liying Wang, Yangmei Li, Xia Xu, Yuqiao Fu, Xin Zhang, Xiumin Zhang, Ming Zhang, Zhekai Zhang, Jing Yan, Qingguo Ye, Jing Wang, Zhe Chen, Charlie Degui Lin, Wei Li, Qing |
description | Currently, the reliable prognostic biomarkers for WHO grade II diffuse astrocytomas (DA) are still limited. We investigated the relations between the level of 5-Hydroxymethylcytosine (5hmC), an oxidated production of 5-methylcytosine (5mC) by the ten eleven translocated (TET) enzymes, and clinicopathological features of glioma patients. With an identified anti-5hmC antibody, we performed immunohistochemistry in 287 glioma cases. We detected that 5hmC variably reduced in most gliomas and 5hmC reduction was closely associated with higher pathological grades and shortened survival of glioma patients. In multivariate analysis, 5hmC had no independent prognostic value in the entire patient cohort. However, multivariate analysis within subtypes of gliomas revealed that 5hmC was still a prognostic marker confined to DA. In addition, we detected that
IDH1
mutation by DNA sequencing was associated with favorable survival within DA. Lastly, we detected that the combination of 5hmC/KI67 was a useful prognostic marker for restratification of DA. |
doi_str_mv | 10.1038/srep20882 |
format | Article |
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IDH1
mutation by DNA sequencing was associated with favorable survival within DA. Lastly, we detected that the combination of 5hmC/KI67 was a useful prognostic marker for restratification of DA.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep20882</identifier><identifier>PMID: 26864347</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/51 ; 5-Methylcytosine - analogs & derivatives ; 692/308/1892 ; 692/4028/67 ; 692/53/2422 ; Adolescent ; Adult ; Aged ; Antibodies - chemistry ; Astrocytoma ; Astrocytoma - diagnosis ; Astrocytoma - metabolism ; Astrocytoma - mortality ; Astrocytoma - pathology ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Brain - metabolism ; Brain - pathology ; Brain tumors ; Central Nervous System Neoplasms - diagnosis ; Central Nervous System Neoplasms - metabolism ; Central Nervous System Neoplasms - mortality ; Central Nervous System Neoplasms - pathology ; Cytosine - analogs & derivatives ; Cytosine - metabolism ; DNA sequencing ; Enzymes ; Female ; Glioma ; Humanities and Social Sciences ; Humans ; Immunohistochemistry ; Isocitrate Dehydrogenase - genetics ; Isocitrate Dehydrogenase - metabolism ; Ki-67 Antigen - genetics ; Ki-67 Antigen - metabolism ; Male ; Medical prognosis ; Middle Aged ; multidisciplinary ; Multivariate analysis ; Mutation ; Neoplasm Grading ; Prognosis ; Science ; Science (multidisciplinary) ; Spinal Cord - metabolism ; Spinal Cord - pathology ; Survival ; Survival Analysis</subject><ispartof>Scientific reports, 2016-02, Vol.6 (1), p.20882-20882, Article 20882</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Feb 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-7df6e1d43489742bfd2ca1cb76b937f053a8950ebdafcb81cf6ac1725de660473</citedby><cites>FETCH-LOGICAL-c438t-7df6e1d43489742bfd2ca1cb76b937f053a8950ebdafcb81cf6ac1725de660473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749994/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749994/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51554,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26864347$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Feng</creatorcontrib><creatorcontrib>Liu, Yifan</creatorcontrib><creatorcontrib>Zhang, Zhiwen</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Wan, Yi</creatorcontrib><creatorcontrib>Zhang, Liying</creatorcontrib><creatorcontrib>Wang, Yangmei</creatorcontrib><creatorcontrib>Li, Xia</creatorcontrib><creatorcontrib>Xu, Yuqiao</creatorcontrib><creatorcontrib>Fu, Xin</creatorcontrib><creatorcontrib>Zhang, Xiumin</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Zhang, Zhekai</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Yan, Qingguo</creatorcontrib><creatorcontrib>Ye, Jing</creatorcontrib><creatorcontrib>Wang, Zhe</creatorcontrib><creatorcontrib>Chen, Charlie Degui</creatorcontrib><creatorcontrib>Lin, Wei</creatorcontrib><creatorcontrib>Li, Qing</creatorcontrib><title>5-hydroxymethylcytosine loss is associated with poor prognosis for patients with WHO grade II diffuse astrocytomas</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Currently, the reliable prognostic biomarkers for WHO grade II diffuse astrocytomas (DA) are still limited. We investigated the relations between the level of 5-Hydroxymethylcytosine (5hmC), an oxidated production of 5-methylcytosine (5mC) by the ten eleven translocated (TET) enzymes, and clinicopathological features of glioma patients. With an identified anti-5hmC antibody, we performed immunohistochemistry in 287 glioma cases. We detected that 5hmC variably reduced in most gliomas and 5hmC reduction was closely associated with higher pathological grades and shortened survival of glioma patients. In multivariate analysis, 5hmC had no independent prognostic value in the entire patient cohort. However, multivariate analysis within subtypes of gliomas revealed that 5hmC was still a prognostic marker confined to DA. In addition, we detected that
IDH1
mutation by DNA sequencing was associated with favorable survival within DA. Lastly, we detected that the combination of 5hmC/KI67 was a useful prognostic marker for restratification of DA.</description><subject>13/51</subject><subject>5-Methylcytosine - analogs & derivatives</subject><subject>692/308/1892</subject><subject>692/4028/67</subject><subject>692/53/2422</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibodies - chemistry</subject><subject>Astrocytoma</subject><subject>Astrocytoma - diagnosis</subject><subject>Astrocytoma - metabolism</subject><subject>Astrocytoma - mortality</subject><subject>Astrocytoma - pathology</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Brain tumors</subject><subject>Central Nervous System Neoplasms - diagnosis</subject><subject>Central Nervous System Neoplasms - metabolism</subject><subject>Central Nervous System Neoplasms - mortality</subject><subject>Central Nervous System Neoplasms - pathology</subject><subject>Cytosine - analogs & derivatives</subject><subject>Cytosine - metabolism</subject><subject>DNA sequencing</subject><subject>Enzymes</subject><subject>Female</subject><subject>Glioma</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Isocitrate Dehydrogenase - genetics</subject><subject>Isocitrate Dehydrogenase - metabolism</subject><subject>Ki-67 Antigen - genetics</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Multivariate analysis</subject><subject>Mutation</subject><subject>Neoplasm Grading</subject><subject>Prognosis</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal Cord - pathology</subject><subject>Survival</subject><subject>Survival Analysis</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkU9vFCEYh4nR2Kb24BcwJF7UZBQYGOBiYprWbtKkF41HwvBnl2ZmGIFR59vLZutmVS5A3ifP-4MXgJcYvceoFR9ycjNBQpAn4JwgyhrSEvL05HwGLnN-QHUxIimWz8EZ6URHW8rPQWLNbrUp_lpHV3brYNYSc5gcHGLOMGSoc44m6OIs_BnKDs4xJjinuJ0ql6Hf33QJbir5AHy7vYfbpK2Dmw20wfslu2opKe7do84vwDOvh-wuH_cL8PXm-svVbXN3_3lz9emuMbQVpeHWdw7bGlNITknvLTEam553vWy5R6zVQjLkequ96QU2vtMGc8Ks6zpEeXsBPh6889KPzpoaMelBzSmMOq0q6qD-rkxhp7bxh6KcSilpFbx5FKT4fXG5qDFk44ZBTy4uWWHeMYwEkqyir_9BH-KSpvo8hYWUqOWcyUq9PVAm1d9Nzh_DYKT2w1THYVb21Wn6I_lndBV4dwByLU1bl05a_mf7Da-Lq-o</recordid><startdate>20160211</startdate><enddate>20160211</enddate><creator>Zhang, Feng</creator><creator>Liu, Yifan</creator><creator>Zhang, Zhiwen</creator><creator>Li, Jie</creator><creator>Wan, Yi</creator><creator>Zhang, Liying</creator><creator>Wang, Yangmei</creator><creator>Li, Xia</creator><creator>Xu, Yuqiao</creator><creator>Fu, Xin</creator><creator>Zhang, Xiumin</creator><creator>Zhang, Ming</creator><creator>Zhang, Zhekai</creator><creator>Zhang, Jing</creator><creator>Yan, Qingguo</creator><creator>Ye, Jing</creator><creator>Wang, Zhe</creator><creator>Chen, Charlie Degui</creator><creator>Lin, Wei</creator><creator>Li, Qing</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160211</creationdate><title>5-hydroxymethylcytosine loss is associated with poor prognosis for patients with WHO grade II diffuse astrocytomas</title><author>Zhang, Feng ; Liu, Yifan ; Zhang, Zhiwen ; Li, Jie ; Wan, Yi ; Zhang, Liying ; Wang, Yangmei ; Li, Xia ; Xu, Yuqiao ; Fu, Xin ; Zhang, Xiumin ; Zhang, Ming ; Zhang, Zhekai ; Zhang, Jing ; Yan, Qingguo ; Ye, Jing ; Wang, Zhe ; Chen, Charlie Degui ; Lin, Wei ; Li, Qing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-7df6e1d43489742bfd2ca1cb76b937f053a8950ebdafcb81cf6ac1725de660473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>13/51</topic><topic>5-Methylcytosine - analogs & derivatives</topic><topic>692/308/1892</topic><topic>692/4028/67</topic><topic>692/53/2422</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibodies - chemistry</topic><topic>Astrocytoma</topic><topic>Astrocytoma - diagnosis</topic><topic>Astrocytoma - metabolism</topic><topic>Astrocytoma - mortality</topic><topic>Astrocytoma - pathology</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Brain tumors</topic><topic>Central Nervous System Neoplasms - diagnosis</topic><topic>Central Nervous System Neoplasms - metabolism</topic><topic>Central Nervous System Neoplasms - mortality</topic><topic>Central Nervous System Neoplasms - pathology</topic><topic>Cytosine - analogs & derivatives</topic><topic>Cytosine - metabolism</topic><topic>DNA sequencing</topic><topic>Enzymes</topic><topic>Female</topic><topic>Glioma</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Isocitrate Dehydrogenase - genetics</topic><topic>Isocitrate Dehydrogenase - metabolism</topic><topic>Ki-67 Antigen - genetics</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>multidisciplinary</topic><topic>Multivariate analysis</topic><topic>Mutation</topic><topic>Neoplasm Grading</topic><topic>Prognosis</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal Cord - pathology</topic><topic>Survival</topic><topic>Survival Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Feng</creatorcontrib><creatorcontrib>Liu, Yifan</creatorcontrib><creatorcontrib>Zhang, Zhiwen</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Wan, Yi</creatorcontrib><creatorcontrib>Zhang, Liying</creatorcontrib><creatorcontrib>Wang, Yangmei</creatorcontrib><creatorcontrib>Li, Xia</creatorcontrib><creatorcontrib>Xu, Yuqiao</creatorcontrib><creatorcontrib>Fu, Xin</creatorcontrib><creatorcontrib>Zhang, Xiumin</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Zhang, Zhekai</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Yan, Qingguo</creatorcontrib><creatorcontrib>Ye, Jing</creatorcontrib><creatorcontrib>Wang, Zhe</creatorcontrib><creatorcontrib>Chen, Charlie Degui</creatorcontrib><creatorcontrib>Lin, Wei</creatorcontrib><creatorcontrib>Li, Qing</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>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>Science Database (Alumni Edition)</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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</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>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</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>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Feng</au><au>Liu, Yifan</au><au>Zhang, Zhiwen</au><au>Li, Jie</au><au>Wan, Yi</au><au>Zhang, Liying</au><au>Wang, Yangmei</au><au>Li, Xia</au><au>Xu, Yuqiao</au><au>Fu, Xin</au><au>Zhang, Xiumin</au><au>Zhang, Ming</au><au>Zhang, Zhekai</au><au>Zhang, Jing</au><au>Yan, Qingguo</au><au>Ye, Jing</au><au>Wang, Zhe</au><au>Chen, Charlie Degui</au><au>Lin, Wei</au><au>Li, Qing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>5-hydroxymethylcytosine loss is associated with poor prognosis for patients with WHO grade II diffuse astrocytomas</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-02-11</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>20882</spage><epage>20882</epage><pages>20882-20882</pages><artnum>20882</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Currently, the reliable prognostic biomarkers for WHO grade II diffuse astrocytomas (DA) are still limited. We investigated the relations between the level of 5-Hydroxymethylcytosine (5hmC), an oxidated production of 5-methylcytosine (5mC) by the ten eleven translocated (TET) enzymes, and clinicopathological features of glioma patients. With an identified anti-5hmC antibody, we performed immunohistochemistry in 287 glioma cases. We detected that 5hmC variably reduced in most gliomas and 5hmC reduction was closely associated with higher pathological grades and shortened survival of glioma patients. In multivariate analysis, 5hmC had no independent prognostic value in the entire patient cohort. However, multivariate analysis within subtypes of gliomas revealed that 5hmC was still a prognostic marker confined to DA. In addition, we detected that
IDH1
mutation by DNA sequencing was associated with favorable survival within DA. Lastly, we detected that the combination of 5hmC/KI67 was a useful prognostic marker for restratification of DA.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26864347</pmid><doi>10.1038/srep20882</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 13/51 5-Methylcytosine - analogs & derivatives 692/308/1892 692/4028/67 692/53/2422 Adolescent Adult Aged Antibodies - chemistry Astrocytoma Astrocytoma - diagnosis Astrocytoma - metabolism Astrocytoma - mortality Astrocytoma - pathology Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Brain - metabolism Brain - pathology Brain tumors Central Nervous System Neoplasms - diagnosis Central Nervous System Neoplasms - metabolism Central Nervous System Neoplasms - mortality Central Nervous System Neoplasms - pathology Cytosine - analogs & derivatives Cytosine - metabolism DNA sequencing Enzymes Female Glioma Humanities and Social Sciences Humans Immunohistochemistry Isocitrate Dehydrogenase - genetics Isocitrate Dehydrogenase - metabolism Ki-67 Antigen - genetics Ki-67 Antigen - metabolism Male Medical prognosis Middle Aged multidisciplinary Multivariate analysis Mutation Neoplasm Grading Prognosis Science Science (multidisciplinary) Spinal Cord - metabolism Spinal Cord - pathology Survival Survival Analysis |
title | 5-hydroxymethylcytosine loss is associated with poor prognosis for patients with WHO grade II diffuse astrocytomas |
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