Diagnostic Value of a Group of MicroRNA Genes Hypermethylated in Ovarian Carcinoma

The study was designed to determine genes of microRNAs hypermethylated in malignant ovarian tumors and to select new diagnostic and prognostic markers of the disease and effective system of markers. Using methyl-specific PCR and a representative sample of 54 ovarian cancer specimens, we determined 5...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Bulletin of experimental biology and medicine 2018-12, Vol.166 (2), p.253-256
Hauptverfasser: Braga, E. A., Loginov, V. I., Filippova, E. A., Burdennyi, A. M., Pronina, I. V., Kazubskaya, T. P., Khodyrev, D. S., Utkin, D. O., Kushlinskii, D. N., Adamyan, L. V., Kuslinskii, N. E.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 256
container_issue 2
container_start_page 253
container_title Bulletin of experimental biology and medicine
container_volume 166
creator Braga, E. A.
Loginov, V. I.
Filippova, E. A.
Burdennyi, A. M.
Pronina, I. V.
Kazubskaya, T. P.
Khodyrev, D. S.
Utkin, D. O.
Kushlinskii, D. N.
Adamyan, L. V.
Kuslinskii, N. E.
description The study was designed to determine genes of microRNAs hypermethylated in malignant ovarian tumors and to select new diagnostic and prognostic markers of the disease and effective system of markers. Using methyl-specific PCR and a representative sample of 54 ovarian cancer specimens, we determined 5 microRNA genes ( MIR-34b/c , MIR-9-1 , MIR-124-3 , MIR-129-2 , and MIR-107 ) hypermethylated in the majority of tumor samples in comparison with paired samples of histologically unchanged tissue (48-57% vs . 4-19%, p
doi_str_mv 10.1007/s10517-018-4326-0
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2139568989</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2139568989</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-9b78addf1c777480cda101b9b841473471f38839207adda6125bb410bb16beee3</originalsourceid><addsrcrecordid>eNp1kF1LwzAUhoMobk5_gDcS8Mab6jlJ16SXMnUT1IGotyFpU-3ox0xaYf_elPkBglf5es6bcx5CjhHOEUBceIQpighQRjFnSQQ7ZIxTwSPJGO6SMQQoiqWUI3Lg_Wo4QoL7ZMQh3DKQY_J4VerXpvVdmdEXXfWWtgXVdO7afj1s78vMtY8Pl3RuG-vpYrO2rrbd26bSnc1p2dDlh3albuhMu6xs2lofkr1CV94efa0T8nxz_TRbRHfL-e3s8i7KuGBdlBohdZ4XmAkhYglZrhHQpEbGGAseCyy4lDxlIAKmE2RTY2IEYzAx1lo-IWfb3LVr33vrO1WXPrNVpRvb9l4x5Ok0kalMA3r6B121vWtCdwMlUxCDtgnBLRVG9t7ZQq1dWWu3UQhqEK62wlUQrgbhCkLNyVdyb2qb_1R8Gw4A2wI-PDWv1v1-_X_qJ0N5iTw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2138907157</pqid></control><display><type>article</type><title>Diagnostic Value of a Group of MicroRNA Genes Hypermethylated in Ovarian Carcinoma</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Braga, E. A. ; Loginov, V. I. ; Filippova, E. A. ; Burdennyi, A. M. ; Pronina, I. V. ; Kazubskaya, T. P. ; Khodyrev, D. S. ; Utkin, D. O. ; Kushlinskii, D. N. ; Adamyan, L. V. ; Kuslinskii, N. E.</creator><creatorcontrib>Braga, E. A. ; Loginov, V. I. ; Filippova, E. A. ; Burdennyi, A. M. ; Pronina, I. V. ; Kazubskaya, T. P. ; Khodyrev, D. S. ; Utkin, D. O. ; Kushlinskii, D. N. ; Adamyan, L. V. ; Kuslinskii, N. E.</creatorcontrib><description>The study was designed to determine genes of microRNAs hypermethylated in malignant ovarian tumors and to select new diagnostic and prognostic markers of the disease and effective system of markers. Using methyl-specific PCR and a representative sample of 54 ovarian cancer specimens, we determined 5 microRNA genes ( MIR-34b/c , MIR-9-1 , MIR-124-3 , MIR-129-2 , and MIR-107 ) hypermethylated in the majority of tumor samples in comparison with paired samples of histologically unchanged tissue (48-57% vs . 4-19%, p &lt;0.001). Using ROC-analysis, we selected an effective system of 4 markers for diagnosis of ovarian cancer ( MIR-9-1 , MIR-124-3 , MIR-129-2 , and MIR-107 ) characterized by high sensitivity and specificity (up to 87-94% at AUC=0.92) relative to the conventional norm (54 paired samples of histologically unchanged tissue) and absolute norm (18 ovarian tissue samples from subjects who died from non-tumor diseases). It was also shown that methylation of MIR-129-2 , MIR-9-1 , and MIR-34b/c genes is significantly ( p &lt;0.01) correlated with the clinical stage or the presence of metastases. The results indicate that epigenetic modifications of the studied microRNA genes are involved in the pathogenesis and progression of ovarian cancer and attest to their diagnostic and prognostic potential.</description><identifier>ISSN: 0007-4888</identifier><identifier>EISSN: 1573-8221</identifier><identifier>DOI: 10.1007/s10517-018-4326-0</identifier><identifier>PMID: 30488208</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adult ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; CpG Islands ; Disease Progression ; DNA Methylation ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Internal Medicine ; Laboratory Medicine ; Lymphatic Metastasis ; Metastases ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Middle Aged ; miRNA ; Neoplasm Staging ; Ovarian cancer ; Ovarian carcinoma ; Ovarian Neoplasms - diagnosis ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Pathology ; Sensitivity and Specificity ; Tumors</subject><ispartof>Bulletin of experimental biology and medicine, 2018-12, Vol.166 (2), p.253-256</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2018</rights><rights>Bulletin of Experimental Biology and Medicine is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-9b78addf1c777480cda101b9b841473471f38839207adda6125bb410bb16beee3</citedby><cites>FETCH-LOGICAL-c372t-9b78addf1c777480cda101b9b841473471f38839207adda6125bb410bb16beee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10517-018-4326-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10517-018-4326-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30488208$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Braga, E. A.</creatorcontrib><creatorcontrib>Loginov, V. I.</creatorcontrib><creatorcontrib>Filippova, E. A.</creatorcontrib><creatorcontrib>Burdennyi, A. M.</creatorcontrib><creatorcontrib>Pronina, I. V.</creatorcontrib><creatorcontrib>Kazubskaya, T. P.</creatorcontrib><creatorcontrib>Khodyrev, D. S.</creatorcontrib><creatorcontrib>Utkin, D. O.</creatorcontrib><creatorcontrib>Kushlinskii, D. N.</creatorcontrib><creatorcontrib>Adamyan, L. V.</creatorcontrib><creatorcontrib>Kuslinskii, N. E.</creatorcontrib><title>Diagnostic Value of a Group of MicroRNA Genes Hypermethylated in Ovarian Carcinoma</title><title>Bulletin of experimental biology and medicine</title><addtitle>Bull Exp Biol Med</addtitle><addtitle>Bull Exp Biol Med</addtitle><description>The study was designed to determine genes of microRNAs hypermethylated in malignant ovarian tumors and to select new diagnostic and prognostic markers of the disease and effective system of markers. Using methyl-specific PCR and a representative sample of 54 ovarian cancer specimens, we determined 5 microRNA genes ( MIR-34b/c , MIR-9-1 , MIR-124-3 , MIR-129-2 , and MIR-107 ) hypermethylated in the majority of tumor samples in comparison with paired samples of histologically unchanged tissue (48-57% vs . 4-19%, p &lt;0.001). Using ROC-analysis, we selected an effective system of 4 markers for diagnosis of ovarian cancer ( MIR-9-1 , MIR-124-3 , MIR-129-2 , and MIR-107 ) characterized by high sensitivity and specificity (up to 87-94% at AUC=0.92) relative to the conventional norm (54 paired samples of histologically unchanged tissue) and absolute norm (18 ovarian tissue samples from subjects who died from non-tumor diseases). It was also shown that methylation of MIR-129-2 , MIR-9-1 , and MIR-34b/c genes is significantly ( p &lt;0.01) correlated with the clinical stage or the presence of metastases. The results indicate that epigenetic modifications of the studied microRNA genes are involved in the pathogenesis and progression of ovarian cancer and attest to their diagnostic and prognostic potential.</description><subject>Adult</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>CpG Islands</subject><subject>Disease Progression</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Laboratory Medicine</subject><subject>Lymphatic Metastasis</subject><subject>Metastases</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Neoplasm Staging</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - diagnosis</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Pathology</subject><subject>Sensitivity and Specificity</subject><subject>Tumors</subject><issn>0007-4888</issn><issn>1573-8221</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kF1LwzAUhoMobk5_gDcS8Mab6jlJ16SXMnUT1IGotyFpU-3ox0xaYf_elPkBglf5es6bcx5CjhHOEUBceIQpighQRjFnSQQ7ZIxTwSPJGO6SMQQoiqWUI3Lg_Wo4QoL7ZMQh3DKQY_J4VerXpvVdmdEXXfWWtgXVdO7afj1s78vMtY8Pl3RuG-vpYrO2rrbd26bSnc1p2dDlh3albuhMu6xs2lofkr1CV94efa0T8nxz_TRbRHfL-e3s8i7KuGBdlBohdZ4XmAkhYglZrhHQpEbGGAseCyy4lDxlIAKmE2RTY2IEYzAx1lo-IWfb3LVr33vrO1WXPrNVpRvb9l4x5Ok0kalMA3r6B121vWtCdwMlUxCDtgnBLRVG9t7ZQq1dWWu3UQhqEK62wlUQrgbhCkLNyVdyb2qb_1R8Gw4A2wI-PDWv1v1-_X_qJ0N5iTw</recordid><startdate>20181201</startdate><enddate>20181201</enddate><creator>Braga, E. A.</creator><creator>Loginov, V. I.</creator><creator>Filippova, E. A.</creator><creator>Burdennyi, A. M.</creator><creator>Pronina, I. V.</creator><creator>Kazubskaya, T. P.</creator><creator>Khodyrev, D. S.</creator><creator>Utkin, D. O.</creator><creator>Kushlinskii, D. N.</creator><creator>Adamyan, L. V.</creator><creator>Kuslinskii, N. E.</creator><general>Springer US</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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20181201</creationdate><title>Diagnostic Value of a Group of MicroRNA Genes Hypermethylated in Ovarian Carcinoma</title><author>Braga, E. A. ; Loginov, V. I. ; Filippova, E. A. ; Burdennyi, A. M. ; Pronina, I. V. ; Kazubskaya, T. P. ; Khodyrev, D. S. ; Utkin, D. O. ; Kushlinskii, D. N. ; Adamyan, L. V. ; Kuslinskii, N. E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-9b78addf1c777480cda101b9b841473471f38839207adda6125bb410bb16beee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>CpG Islands</topic><topic>Disease Progression</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Laboratory Medicine</topic><topic>Lymphatic Metastasis</topic><topic>Metastases</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Neoplasm Staging</topic><topic>Ovarian cancer</topic><topic>Ovarian carcinoma</topic><topic>Ovarian Neoplasms - diagnosis</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Pathology</topic><topic>Sensitivity and Specificity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Braga, E. A.</creatorcontrib><creatorcontrib>Loginov, V. I.</creatorcontrib><creatorcontrib>Filippova, E. A.</creatorcontrib><creatorcontrib>Burdennyi, A. M.</creatorcontrib><creatorcontrib>Pronina, I. V.</creatorcontrib><creatorcontrib>Kazubskaya, T. P.</creatorcontrib><creatorcontrib>Khodyrev, D. S.</creatorcontrib><creatorcontrib>Utkin, D. O.</creatorcontrib><creatorcontrib>Kushlinskii, D. N.</creatorcontrib><creatorcontrib>Adamyan, L. V.</creatorcontrib><creatorcontrib>Kuslinskii, N. E.</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>Health &amp; 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>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 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 &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science 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 China</collection><collection>MEDLINE - Academic</collection><jtitle>Bulletin of experimental biology and medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Braga, E. A.</au><au>Loginov, V. I.</au><au>Filippova, E. A.</au><au>Burdennyi, A. M.</au><au>Pronina, I. V.</au><au>Kazubskaya, T. P.</au><au>Khodyrev, D. S.</au><au>Utkin, D. O.</au><au>Kushlinskii, D. N.</au><au>Adamyan, L. V.</au><au>Kuslinskii, N. E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diagnostic Value of a Group of MicroRNA Genes Hypermethylated in Ovarian Carcinoma</atitle><jtitle>Bulletin of experimental biology and medicine</jtitle><stitle>Bull Exp Biol Med</stitle><addtitle>Bull Exp Biol Med</addtitle><date>2018-12-01</date><risdate>2018</risdate><volume>166</volume><issue>2</issue><spage>253</spage><epage>256</epage><pages>253-256</pages><issn>0007-4888</issn><eissn>1573-8221</eissn><abstract>The study was designed to determine genes of microRNAs hypermethylated in malignant ovarian tumors and to select new diagnostic and prognostic markers of the disease and effective system of markers. Using methyl-specific PCR and a representative sample of 54 ovarian cancer specimens, we determined 5 microRNA genes ( MIR-34b/c , MIR-9-1 , MIR-124-3 , MIR-129-2 , and MIR-107 ) hypermethylated in the majority of tumor samples in comparison with paired samples of histologically unchanged tissue (48-57% vs . 4-19%, p &lt;0.001). Using ROC-analysis, we selected an effective system of 4 markers for diagnosis of ovarian cancer ( MIR-9-1 , MIR-124-3 , MIR-129-2 , and MIR-107 ) characterized by high sensitivity and specificity (up to 87-94% at AUC=0.92) relative to the conventional norm (54 paired samples of histologically unchanged tissue) and absolute norm (18 ovarian tissue samples from subjects who died from non-tumor diseases). It was also shown that methylation of MIR-129-2 , MIR-9-1 , and MIR-34b/c genes is significantly ( p &lt;0.01) correlated with the clinical stage or the presence of metastases. The results indicate that epigenetic modifications of the studied microRNA genes are involved in the pathogenesis and progression of ovarian cancer and attest to their diagnostic and prognostic potential.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>30488208</pmid><doi>10.1007/s10517-018-4326-0</doi><tpages>4</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0007-4888
ispartof Bulletin of experimental biology and medicine, 2018-12, Vol.166 (2), p.253-256
issn 0007-4888
1573-8221
language eng
recordid cdi_proquest_miscellaneous_2139568989
source MEDLINE; Springer Nature - Complete Springer Journals
subjects Adult
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Biomedical and Life Sciences
Biomedicine
Cell Biology
CpG Islands
Disease Progression
DNA Methylation
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic
Humans
Internal Medicine
Laboratory Medicine
Lymphatic Metastasis
Metastases
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
miRNA
Neoplasm Staging
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - diagnosis
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Pathology
Sensitivity and Specificity
Tumors
title Diagnostic Value of a Group of MicroRNA Genes Hypermethylated in Ovarian Carcinoma
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T04%3A08%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Diagnostic%20Value%20of%20a%20Group%20of%20MicroRNA%20Genes%20Hypermethylated%20in%20Ovarian%20Carcinoma&rft.jtitle=Bulletin%20of%20experimental%20biology%20and%20medicine&rft.au=Braga,%20E.%20A.&rft.date=2018-12-01&rft.volume=166&rft.issue=2&rft.spage=253&rft.epage=256&rft.pages=253-256&rft.issn=0007-4888&rft.eissn=1573-8221&rft_id=info:doi/10.1007/s10517-018-4326-0&rft_dat=%3Cproquest_cross%3E2139568989%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2138907157&rft_id=info:pmid/30488208&rfr_iscdi=true