Downregulation of p21 in myelodysplastic syndrome is associated with p73 promoter hypermethylation and indicates poor prognosis
p21 Can both promote and inhibit tumorigenic processes. We explored the role of p21 in myelodysplastic syndrome (MDS). In this study, we analyzed p21 expression and p73 methylation in 88 patients with de novo MDS. We found decreased expression of the p21 gene in higher-risk MDS compared with lower-r...
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| Veröffentlicht in: | American journal of clinical pathology 2013-12, Vol.140 (6), p.819-827 |
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| container_title | American journal of clinical pathology |
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| creator | Zhao, Youshan Guo, Juan Zhang, Xi Zhang, Zheng Gu, Shucheng Fei, Chengmin Li, Xiao Chang, Chunkang |
| description | p21 Can both promote and inhibit tumorigenic processes. We explored the role of p21 in myelodysplastic syndrome (MDS).
In this study, we analyzed p21 expression and p73 methylation in 88 patients with de novo MDS.
We found decreased expression of the p21 gene in higher-risk MDS compared with lower-risk groups or healthy controls (P < .05). Patients with p73 methylation had lower p21 than those in the unmethylated group (P < .001). Moreover, there was a significantly positive correlation between p73 and p21 expression in MDS (r = 0.436, P < .001). In vitro assays further confirm the role of p73 methylation in p21 expression. Compared with patients with normal expression levels of p21, patients with lower p21 expression levels experienced much higher rates of transformation to acute myeloid leukemia and lower overall survival both in univariate as well as multivariate analyses.
Our results suggest p21 expression may serve as a new biomarker to predict clinical outcome in patients with MDS. |
| doi_str_mv | 10.1309/AJCPZ5E6IWPWSZXE |
| format | Article |
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In this study, we analyzed p21 expression and p73 methylation in 88 patients with de novo MDS.
We found decreased expression of the p21 gene in higher-risk MDS compared with lower-risk groups or healthy controls (P < .05). Patients with p73 methylation had lower p21 than those in the unmethylated group (P < .001). Moreover, there was a significantly positive correlation between p73 and p21 expression in MDS (r = 0.436, P < .001). In vitro assays further confirm the role of p73 methylation in p21 expression. Compared with patients with normal expression levels of p21, patients with lower p21 expression levels experienced much higher rates of transformation to acute myeloid leukemia and lower overall survival both in univariate as well as multivariate analyses.
Our results suggest p21 expression may serve as a new biomarker to predict clinical outcome in patients with MDS.</description><identifier>ISSN: 0002-9173</identifier><identifier>EISSN: 1943-7722</identifier><identifier>DOI: 10.1309/AJCPZ5E6IWPWSZXE</identifier><identifier>PMID: 24225749</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Blotting, Western ; Cyclin-Dependent Kinase Inhibitor p21 - metabolism ; Disease Progression ; DNA Methylation ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Down-Regulation ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Myelodysplastic Syndromes - genetics ; Myelodysplastic Syndromes - metabolism ; Myelodysplastic Syndromes - mortality ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Prognosis ; Promoter Regions, Genetic ; Proportional Hazards Models ; Real-Time Polymerase Chain Reaction ; Tumor Protein p73 ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Young Adult</subject><ispartof>American journal of clinical pathology, 2013-12, Vol.140 (6), p.819-827</ispartof><rights>Copyright American Society for Clinical Pathology Dec 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c369t-a4a832009550f5aaa102d3e19e56849b27853bea4d47ebc1e98efbdb07b41c083</citedby><cites>FETCH-LOGICAL-c369t-a4a832009550f5aaa102d3e19e56849b27853bea4d47ebc1e98efbdb07b41c083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24225749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Youshan</creatorcontrib><creatorcontrib>Guo, Juan</creatorcontrib><creatorcontrib>Zhang, Xi</creatorcontrib><creatorcontrib>Zhang, Zheng</creatorcontrib><creatorcontrib>Gu, Shucheng</creatorcontrib><creatorcontrib>Fei, Chengmin</creatorcontrib><creatorcontrib>Li, Xiao</creatorcontrib><creatorcontrib>Chang, Chunkang</creatorcontrib><title>Downregulation of p21 in myelodysplastic syndrome is associated with p73 promoter hypermethylation and indicates poor prognosis</title><title>American journal of clinical pathology</title><addtitle>Am J Clin Pathol</addtitle><description>p21 Can both promote and inhibit tumorigenic processes. We explored the role of p21 in myelodysplastic syndrome (MDS).
In this study, we analyzed p21 expression and p73 methylation in 88 patients with de novo MDS.
We found decreased expression of the p21 gene in higher-risk MDS compared with lower-risk groups or healthy controls (P < .05). Patients with p73 methylation had lower p21 than those in the unmethylated group (P < .001). Moreover, there was a significantly positive correlation between p73 and p21 expression in MDS (r = 0.436, P < .001). In vitro assays further confirm the role of p73 methylation in p21 expression. Compared with patients with normal expression levels of p21, patients with lower p21 expression levels experienced much higher rates of transformation to acute myeloid leukemia and lower overall survival both in univariate as well as multivariate analyses.
Our results suggest p21 expression may serve as a new biomarker to predict clinical outcome in patients with MDS.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor</subject><subject>Blotting, Western</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</subject><subject>Disease Progression</subject><subject>DNA Methylation</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myelodysplastic Syndromes - genetics</subject><subject>Myelodysplastic Syndromes - metabolism</subject><subject>Myelodysplastic Syndromes - mortality</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Prognosis</subject><subject>Promoter Regions, Genetic</subject><subject>Proportional Hazards Models</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Tumor Protein p73</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Young Adult</subject><issn>0002-9173</issn><issn>1943-7722</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><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>eNpdkUtr3DAURkVJaSZp910VQTbZuNXLDy3DZPIogQTSMmU2RrauZxRsy9G1CV7lr1ch0y5mpcU937nifoR85ew7l0z_uPi5fNikq-x2_bB-3PxZfSALrpVM8lyII7JgjIlE81wekxPEJ8a4KJj6RI6FEiLNlV6Q10v_0gfYTq0Zne-pb-ggOHU97WZovZ1xaA2OrqY49zb4DqhDahB97cwIlr64cUeHXNIhDv0Ige7mAUIH427eO01vo9C6OgaQDt6HN3jbe3T4mXxsTIvwZf-ekt9Xq1_Lm-Tu_vp2eXGX1DLTY2KUKaRgTKcpa1JjDGfCSuAa0qxQuhJ5kcoKjLIqh6rmoAtoKluxvFK8ZoU8Jefv3rj5eQIcy85hDW1revATllylmmdcah7RswP0yU-hj7-LlNZFJuNdI8XeqTp4xABNOQTXmTCXnJVv5ZSH5cTIt714qjqw_wP_2pB_AcNEjl0</recordid><startdate>201312</startdate><enddate>201312</enddate><creator>Zhao, Youshan</creator><creator>Guo, Juan</creator><creator>Zhang, Xi</creator><creator>Zhang, Zheng</creator><creator>Gu, Shucheng</creator><creator>Fei, Chengmin</creator><creator>Li, Xiao</creator><creator>Chang, Chunkang</creator><general>Oxford University Press</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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>201312</creationdate><title>Downregulation of p21 in myelodysplastic syndrome is associated with p73 promoter hypermethylation and indicates poor prognosis</title><author>Zhao, Youshan ; Guo, Juan ; Zhang, Xi ; Zhang, Zheng ; Gu, Shucheng ; Fei, Chengmin ; Li, Xiao ; Chang, Chunkang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c369t-a4a832009550f5aaa102d3e19e56849b27853bea4d47ebc1e98efbdb07b41c083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor</topic><topic>Blotting, Western</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</topic><topic>Disease Progression</topic><topic>DNA Methylation</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myelodysplastic Syndromes - genetics</topic><topic>Myelodysplastic Syndromes - metabolism</topic><topic>Myelodysplastic Syndromes - mortality</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Prognosis</topic><topic>Promoter Regions, Genetic</topic><topic>Proportional Hazards Models</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Tumor Protein p73</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Youshan</creatorcontrib><creatorcontrib>Guo, Juan</creatorcontrib><creatorcontrib>Zhang, Xi</creatorcontrib><creatorcontrib>Zhang, Zheng</creatorcontrib><creatorcontrib>Gu, Shucheng</creatorcontrib><creatorcontrib>Fei, Chengmin</creatorcontrib><creatorcontrib>Li, Xiao</creatorcontrib><creatorcontrib>Chang, Chunkang</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>ProQuest Nursing and Allied Health Journals</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical 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)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</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>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Biological Science Journals</collection><collection>Nursing & Allied Health Premium</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>MEDLINE - Academic</collection><jtitle>American journal of clinical pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Youshan</au><au>Guo, Juan</au><au>Zhang, Xi</au><au>Zhang, Zheng</au><au>Gu, Shucheng</au><au>Fei, Chengmin</au><au>Li, Xiao</au><au>Chang, Chunkang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of p21 in myelodysplastic syndrome is associated with p73 promoter hypermethylation and indicates poor prognosis</atitle><jtitle>American journal of clinical pathology</jtitle><addtitle>Am J Clin Pathol</addtitle><date>2013-12</date><risdate>2013</risdate><volume>140</volume><issue>6</issue><spage>819</spage><epage>827</epage><pages>819-827</pages><issn>0002-9173</issn><eissn>1943-7722</eissn><abstract>p21 Can both promote and inhibit tumorigenic processes. We explored the role of p21 in myelodysplastic syndrome (MDS).
In this study, we analyzed p21 expression and p73 methylation in 88 patients with de novo MDS.
We found decreased expression of the p21 gene in higher-risk MDS compared with lower-risk groups or healthy controls (P < .05). Patients with p73 methylation had lower p21 than those in the unmethylated group (P < .001). Moreover, there was a significantly positive correlation between p73 and p21 expression in MDS (r = 0.436, P < .001). In vitro assays further confirm the role of p73 methylation in p21 expression. Compared with patients with normal expression levels of p21, patients with lower p21 expression levels experienced much higher rates of transformation to acute myeloid leukemia and lower overall survival both in univariate as well as multivariate analyses.
Our results suggest p21 expression may serve as a new biomarker to predict clinical outcome in patients with MDS.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>24225749</pmid><doi>10.1309/AJCPZ5E6IWPWSZXE</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Biomarkers, Tumor Blotting, Western Cyclin-Dependent Kinase Inhibitor p21 - metabolism Disease Progression DNA Methylation DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Down-Regulation Female Humans Kaplan-Meier Estimate Male Middle Aged Myelodysplastic Syndromes - genetics Myelodysplastic Syndromes - metabolism Myelodysplastic Syndromes - mortality Nuclear Proteins - genetics Nuclear Proteins - metabolism Prognosis Promoter Regions, Genetic Proportional Hazards Models Real-Time Polymerase Chain Reaction Tumor Protein p73 Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Young Adult |
| title | Downregulation of p21 in myelodysplastic syndrome is associated with p73 promoter hypermethylation and indicates poor prognosis |
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