NDRG2 and NDRG4 Expression Is Altered in Glioblastoma and Influences Survival in Patients with MGMT-methylated Tumors
The N-myc down-regulated gene (NDRG) family is a group of genes that have predominantly tumor-suppressive effects. The goal of this study was to investigate the expression of NDRG2 and NDRG4 in surgical specimens of human glioblastoma and in normal brain tissue, and to search for correlations with o...
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Veröffentlicht in: | Anticancer research 2016-03, Vol.36 (3), p.887-897 |
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description | The N-myc down-regulated gene (NDRG) family is a group of genes that have predominantly tumor-suppressive effects. The goal of this study was to investigate the expression of NDRG2 and NDRG4 in surgical specimens of human glioblastoma and in normal brain tissue, and to search for correlations with overall (OS) and progression-free survival (PFS).
Samples from 44 patients (31 males, 13 females; mean age±SD=57.4±15.7 years) with primary (n=40) or recurrent glioblastoma (n=4) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, with dimensionless semiquantitative immunoreactivity score (IRS), ranging from 0-30] for expression of NDRG2 and NDRG4. Five non-tumorous autopsy brain specimens were used as controls.
On the protein level, expression of NDRG2 was significantly down-regulated in glioblastoma (IRS=3.5±3.0 vs. 8.8±3.3; p=0.001), while expression of NDRG4 was significantly up-regulated (IRS=5.4±3.7 vs. 0.75±0.4 vs, p |
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Samples from 44 patients (31 males, 13 females; mean age±SD=57.4±15.7 years) with primary (n=40) or recurrent glioblastoma (n=4) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, with dimensionless semiquantitative immunoreactivity score (IRS), ranging from 0-30] for expression of NDRG2 and NDRG4. Five non-tumorous autopsy brain specimens were used as controls.
On the protein level, expression of NDRG2 was significantly down-regulated in glioblastoma (IRS=3.5±3.0 vs. 8.8±3.3; p=0.001), while expression of NDRG4 was significantly up-regulated (IRS=5.4±3.7 vs. 0.75±0.4 vs, p<0.001). There was no statistically significant difference in PFS between a group of 15 patients with glioblastoma with MGMT methylation and enhanced expression of NDRG4 mRNA who were treated with adjuvant radiochemotherapy (temozolomide and 60 Gy) and a group of patients with low expression of NDRG4 mRNA [10 (range=5.5-14.2) months vs. 21 (range=10.7-31.3) months] (p=0.13).
Expression of both NDRG2 and NDRG4 genes is significantly altered in glioblastomas. PFS among the patients with glioblastoma with MGMT methylation treated with radiochemotherapy differed significantly in high-expression groups compared to patients without MGMT methlation and without radiochemotherapy (p<0.05).</description><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 26976975</identifier><language>eng</language><publisher>Greece</publisher><subject>Adult ; Aged ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Brain Neoplasms - mortality ; Brain Neoplasms - therapy ; Chemoradiotherapy, Adjuvant ; DNA Methylation ; DNA Modification Methylases - genetics ; DNA Repair Enzymes - genetics ; Female ; Gene Expression Regulation, Neoplastic ; Glioblastoma - genetics ; Glioblastoma - metabolism ; Glioblastoma - mortality ; Glioblastoma - therapy ; Humans ; Male ; Middle Aged ; Muscle Proteins - genetics ; Muscle Proteins - metabolism ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Prognosis ; Survival Analysis ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism</subject><ispartof>Anticancer research, 2016-03, Vol.36 (3), p.887-897</ispartof><rights>Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26976975$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kolodziej, Malgorzata A</creatorcontrib><creatorcontrib>Weischer, Cornelia</creatorcontrib><creatorcontrib>Reinges, Marcus H T</creatorcontrib><creatorcontrib>Uhl, Eberhard</creatorcontrib><creatorcontrib>Weigand, Marcus A</creatorcontrib><creatorcontrib>Schwarm, Frank P</creatorcontrib><creatorcontrib>Schänzer, Anne</creatorcontrib><creatorcontrib>Acker, Till</creatorcontrib><creatorcontrib>Quint, Karl</creatorcontrib><creatorcontrib>Uhle, Florian</creatorcontrib><creatorcontrib>Stein, Marco</creatorcontrib><title>NDRG2 and NDRG4 Expression Is Altered in Glioblastoma and Influences Survival in Patients with MGMT-methylated Tumors</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>The N-myc down-regulated gene (NDRG) family is a group of genes that have predominantly tumor-suppressive effects. The goal of this study was to investigate the expression of NDRG2 and NDRG4 in surgical specimens of human glioblastoma and in normal brain tissue, and to search for correlations with overall (OS) and progression-free survival (PFS).
Samples from 44 patients (31 males, 13 females; mean age±SD=57.4±15.7 years) with primary (n=40) or recurrent glioblastoma (n=4) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, with dimensionless semiquantitative immunoreactivity score (IRS), ranging from 0-30] for expression of NDRG2 and NDRG4. Five non-tumorous autopsy brain specimens were used as controls.
On the protein level, expression of NDRG2 was significantly down-regulated in glioblastoma (IRS=3.5±3.0 vs. 8.8±3.3; p=0.001), while expression of NDRG4 was significantly up-regulated (IRS=5.4±3.7 vs. 0.75±0.4 vs, p<0.001). There was no statistically significant difference in PFS between a group of 15 patients with glioblastoma with MGMT methylation and enhanced expression of NDRG4 mRNA who were treated with adjuvant radiochemotherapy (temozolomide and 60 Gy) and a group of patients with low expression of NDRG4 mRNA [10 (range=5.5-14.2) months vs. 21 (range=10.7-31.3) months] (p=0.13).
Expression of both NDRG2 and NDRG4 genes is significantly altered in glioblastomas. PFS among the patients with glioblastoma with MGMT methylation treated with radiochemotherapy differed significantly in high-expression groups compared to patients without MGMT methlation and without radiochemotherapy (p<0.05).</description><subject>Adult</subject><subject>Aged</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - mortality</subject><subject>Brain Neoplasms - therapy</subject><subject>Chemoradiotherapy, Adjuvant</subject><subject>DNA Methylation</subject><subject>DNA Modification Methylases - genetics</subject><subject>DNA Repair Enzymes - genetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Glioblastoma - genetics</subject><subject>Glioblastoma - metabolism</subject><subject>Glioblastoma - mortality</subject><subject>Glioblastoma - therapy</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Muscle Proteins - genetics</subject><subject>Muscle Proteins - metabolism</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Prognosis</subject><subject>Survival Analysis</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kNFLwzAYxIsgbk7_BcmjL4U2afM1j2POOthUdD6XdPnKImlak3S6_96qEw7uOH7cw51F0xREGkPOkkl06f17knAuCnYRTSgXMCqfRsPj3UtJibSK_KSMLL96h97rzpKVJ3MT0KEi2pLS6K420oeulb_8yjZmQLtDT14Hd9AHaX64Zxk02uDJpw57sik327jFsD8aGcah7dB2zl9F5400Hq9PPove7pfbxUO8fipXi_k67mmahpjXAphkgsEuByzyhmeKqTpTghZAaa04pZLRGigfWwppU2PayARGcSwyNotu_3Z7130M6EPVar9DY6TFbvBVCsCKpAAQI3pzQoe6RVX1TrfSHav_q9g3d_1jvA</recordid><startdate>201603</startdate><enddate>201603</enddate><creator>Kolodziej, Malgorzata A</creator><creator>Weischer, Cornelia</creator><creator>Reinges, Marcus H T</creator><creator>Uhl, Eberhard</creator><creator>Weigand, Marcus A</creator><creator>Schwarm, Frank P</creator><creator>Schänzer, Anne</creator><creator>Acker, Till</creator><creator>Quint, Karl</creator><creator>Uhle, Florian</creator><creator>Stein, Marco</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201603</creationdate><title>NDRG2 and NDRG4 Expression Is Altered in Glioblastoma and Influences Survival in Patients with MGMT-methylated Tumors</title><author>Kolodziej, Malgorzata A ; Weischer, Cornelia ; Reinges, Marcus H T ; Uhl, Eberhard ; Weigand, Marcus A ; Schwarm, Frank P ; Schänzer, Anne ; Acker, Till ; Quint, Karl ; Uhle, Florian ; Stein, Marco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p211t-6b973a3937c57e85f64d3db4d928722bd622a32b726db4271fbe1fa07a076e843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain Neoplasms - mortality</topic><topic>Brain Neoplasms - therapy</topic><topic>Chemoradiotherapy, Adjuvant</topic><topic>DNA Methylation</topic><topic>DNA Modification Methylases - genetics</topic><topic>DNA Repair Enzymes - genetics</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Glioblastoma - genetics</topic><topic>Glioblastoma - metabolism</topic><topic>Glioblastoma - mortality</topic><topic>Glioblastoma - therapy</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Muscle Proteins - genetics</topic><topic>Muscle Proteins - metabolism</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Prognosis</topic><topic>Survival Analysis</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kolodziej, Malgorzata A</creatorcontrib><creatorcontrib>Weischer, Cornelia</creatorcontrib><creatorcontrib>Reinges, Marcus H T</creatorcontrib><creatorcontrib>Uhl, Eberhard</creatorcontrib><creatorcontrib>Weigand, Marcus A</creatorcontrib><creatorcontrib>Schwarm, Frank P</creatorcontrib><creatorcontrib>Schänzer, Anne</creatorcontrib><creatorcontrib>Acker, Till</creatorcontrib><creatorcontrib>Quint, Karl</creatorcontrib><creatorcontrib>Uhle, Florian</creatorcontrib><creatorcontrib>Stein, Marco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kolodziej, Malgorzata A</au><au>Weischer, Cornelia</au><au>Reinges, Marcus H T</au><au>Uhl, Eberhard</au><au>Weigand, Marcus A</au><au>Schwarm, Frank P</au><au>Schänzer, Anne</au><au>Acker, Till</au><au>Quint, Karl</au><au>Uhle, Florian</au><au>Stein, Marco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NDRG2 and NDRG4 Expression Is Altered in Glioblastoma and Influences Survival in Patients with MGMT-methylated Tumors</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2016-03</date><risdate>2016</risdate><volume>36</volume><issue>3</issue><spage>887</spage><epage>897</epage><pages>887-897</pages><eissn>1791-7530</eissn><abstract>The N-myc down-regulated gene (NDRG) family is a group of genes that have predominantly tumor-suppressive effects. The goal of this study was to investigate the expression of NDRG2 and NDRG4 in surgical specimens of human glioblastoma and in normal brain tissue, and to search for correlations with overall (OS) and progression-free survival (PFS).
Samples from 44 patients (31 males, 13 females; mean age±SD=57.4±15.7 years) with primary (n=40) or recurrent glioblastoma (n=4) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, with dimensionless semiquantitative immunoreactivity score (IRS), ranging from 0-30] for expression of NDRG2 and NDRG4. Five non-tumorous autopsy brain specimens were used as controls.
On the protein level, expression of NDRG2 was significantly down-regulated in glioblastoma (IRS=3.5±3.0 vs. 8.8±3.3; p=0.001), while expression of NDRG4 was significantly up-regulated (IRS=5.4±3.7 vs. 0.75±0.4 vs, p<0.001). There was no statistically significant difference in PFS between a group of 15 patients with glioblastoma with MGMT methylation and enhanced expression of NDRG4 mRNA who were treated with adjuvant radiochemotherapy (temozolomide and 60 Gy) and a group of patients with low expression of NDRG4 mRNA [10 (range=5.5-14.2) months vs. 21 (range=10.7-31.3) months] (p=0.13).
Expression of both NDRG2 and NDRG4 genes is significantly altered in glioblastomas. PFS among the patients with glioblastoma with MGMT methylation treated with radiochemotherapy differed significantly in high-expression groups compared to patients without MGMT methlation and without radiochemotherapy (p<0.05).</abstract><cop>Greece</cop><pmid>26976975</pmid><tpages>11</tpages></addata></record> |
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subjects | Adult Aged Brain Neoplasms - genetics Brain Neoplasms - metabolism Brain Neoplasms - mortality Brain Neoplasms - therapy Chemoradiotherapy, Adjuvant DNA Methylation DNA Modification Methylases - genetics DNA Repair Enzymes - genetics Female Gene Expression Regulation, Neoplastic Glioblastoma - genetics Glioblastoma - metabolism Glioblastoma - mortality Glioblastoma - therapy Humans Male Middle Aged Muscle Proteins - genetics Muscle Proteins - metabolism Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Prognosis Survival Analysis Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism |
title | NDRG2 and NDRG4 Expression Is Altered in Glioblastoma and Influences Survival in Patients with MGMT-methylated Tumors |
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