IP6K2 predicts favorable clinical outcome of primary breast cancer
The inositol hexakisphosphate kinase ( ) 1 and 2 genes are localized at 3p21.31, a highly altered gene-dense chromosomal region in cancer. The IP6Ks convert IP6 to IP7, which inhibits activation of the tumor-promoting PI3K/Akt/mTOR signaling pathway. IP6K2 has been suggested to be involved in p53-in...
Gespeichert in:
| Veröffentlicht in: | Molecular and clinical oncology 2021-05, Vol.14 (5), p.94-94, Article 94 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 94 |
|---|---|
| container_issue | 5 |
| container_start_page | 94 |
| container_title | Molecular and clinical oncology |
| container_volume | 14 |
| creator | Sandström, Josefine Balian, Alien Lockowandt, Rebecca Fornander, Tommy Nordenskjöld, Bo Lindström, Linda Pérez-Tenorio, Gizeh Stål, Olle |
| description | The inositol hexakisphosphate kinase (
) 1 and 2 genes are localized at 3p21.31, a highly altered gene-dense chromosomal region in cancer. The IP6Ks convert IP6 to IP7, which inhibits activation of the tumor-promoting PI3K/Akt/mTOR signaling pathway. IP6K2 has been suggested to be involved in p53-induced apoptosis, while IP6K1 may stimulate tumor growth and migration. The present study aimed to elucidate the role of the two IP6Ks in predicting outcome in patients with breast cancer. To the best of our knowledge, the role of IP6K was analyzed for the first time in tumors from three cohorts of patients with breast cancer; one Swedish low-risk cohort, one Dutch cohort and the TCGA dataset. Analyses of gene -and protein expression and subcellular localization were included. IP6K2 gene expression was associated with ER positivity and nuclear p-Akt. Improved prognosis was detected with high IP6K2 gene expression compared with low IP6K2 gene expression in systemically untreated patients in the Swedish low-risk and Dutch cohorts. In the TCGA dataset, IP6K2 prognostic value was significant when selecting for tumors with wild-type
. A multivariable analysis testing IP6K2 against other cancer-related genes at 3p.21.31, including IP6K1 and clinical biomarkers, revealed that IP6K2 was associated with decreased risk of distant recurrence. IP6K1 was associated with increased risk of distant recurrence in the multivariable test and protein analysis revealed trends of worse prognosis with high IP6K1 in the cytoplasm. The expression levels of IP6K1 and IP6K2 were associated to a high extent; however, a diverging prognostic value of the two genes was observed in breast cancer. The present data suggest that IP6K2 can be a favorable prognostic factor, while IP6K1 may not be. |
| doi_str_mv | 10.3892/mco.2021.2256 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_463298</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A657951344</galeid><sourcerecordid>A657951344</sourcerecordid><originalsourceid>FETCH-LOGICAL-c558t-99ea06a21e2a3c978ed23d83af1e36db1b00b8ff32bf322b706d7b46f63c1aa13</originalsourceid><addsrcrecordid>eNp9kstv1DAQxi0EotXSI1cUiQuXLH4kflyQlpZHRSU4AFfLccaLixMXOyniv8dRw8IihC3Lo_HvG9ujD6HHBG-ZVPT5YOOWYkq2lLb8HjqluFG1ari6f4hbfILOcr7GZSiBaaseohPGBBeSs1P08vIDf0ermwS9t1OunLmNyXQBKhv86K0JVZwnGweooiuYH0z6UXUJTJ4qa0YL6RF64EzIcLbuG_Tp9auP52_rq_dvLs93V7VtWznVSoHB3FAC1DCrhISesl4y4wgw3nekw7iTzjHalUU7gXkvuoY7ziwxhrANqu_q5u9wM3d6fYyOxus19bVEoBvOqJL_5S_8552Oaa-DnzURRbHwL-74Ag_QWxinZMKR7Phk9F_0Pt5qoUTR41Lg2VogxW8z5EkPPlsIwYwQ56xpizmVjJbGb9DTv9DrOKextG-hhJRcUfmb2psA2o8ulnvtUlTveCtUS1jTFGr7D6rMHgZv4wjOl_yRYG2MTTHnBO7wR4L14itdfKUXX-nFV4V_8mdjDvQvF7Gf0s7H4Q</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2507886928</pqid></control><display><type>article</type><title>IP6K2 predicts favorable clinical outcome of primary breast cancer</title><source>Spandidos Publications Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>SWEPUB Freely available online</source><creator>Sandström, Josefine ; Balian, Alien ; Lockowandt, Rebecca ; Fornander, Tommy ; Nordenskjöld, Bo ; Lindström, Linda ; Pérez-Tenorio, Gizeh ; Stål, Olle</creator><creatorcontrib>Sandström, Josefine ; Balian, Alien ; Lockowandt, Rebecca ; Fornander, Tommy ; Nordenskjöld, Bo ; Lindström, Linda ; Pérez-Tenorio, Gizeh ; Stål, Olle</creatorcontrib><description>The inositol hexakisphosphate kinase (
) 1 and 2 genes are localized at 3p21.31, a highly altered gene-dense chromosomal region in cancer. The IP6Ks convert IP6 to IP7, which inhibits activation of the tumor-promoting PI3K/Akt/mTOR signaling pathway. IP6K2 has been suggested to be involved in p53-induced apoptosis, while IP6K1 may stimulate tumor growth and migration. The present study aimed to elucidate the role of the two IP6Ks in predicting outcome in patients with breast cancer. To the best of our knowledge, the role of IP6K was analyzed for the first time in tumors from three cohorts of patients with breast cancer; one Swedish low-risk cohort, one Dutch cohort and the TCGA dataset. Analyses of gene -and protein expression and subcellular localization were included. IP6K2 gene expression was associated with ER positivity and nuclear p-Akt. Improved prognosis was detected with high IP6K2 gene expression compared with low IP6K2 gene expression in systemically untreated patients in the Swedish low-risk and Dutch cohorts. In the TCGA dataset, IP6K2 prognostic value was significant when selecting for tumors with wild-type
. A multivariable analysis testing IP6K2 against other cancer-related genes at 3p.21.31, including IP6K1 and clinical biomarkers, revealed that IP6K2 was associated with decreased risk of distant recurrence. IP6K1 was associated with increased risk of distant recurrence in the multivariable test and protein analysis revealed trends of worse prognosis with high IP6K1 in the cytoplasm. The expression levels of IP6K1 and IP6K2 were associated to a high extent; however, a diverging prognostic value of the two genes was observed in breast cancer. The present data suggest that IP6K2 can be a favorable prognostic factor, while IP6K1 may not be.</description><identifier>ISSN: 2049-9450</identifier><identifier>ISSN: 2049-9469</identifier><identifier>EISSN: 2049-9469</identifier><identifier>DOI: 10.3892/mco.2021.2256</identifier><identifier>PMID: 33767863</identifier><language>eng</language><publisher>England: Spandidos Publications</publisher><subject>Antibodies ; Apoptosis ; Breast cancer ; Cancer ; Cancer patients ; Care and treatment ; Clinical outcomes ; Ethnicity ; Gene expression ; Genes ; Genetic aspects ; Genomics ; Inositol ; Kinases ; Medical prognosis ; Medical research ; Medicine, Experimental ; Oncology ; Patient outcomes ; Patients ; Prognosis ; Protein expression ; Proteins ; Software ; Tumor proteins ; Tumors</subject><ispartof>Molecular and clinical oncology, 2021-05, Vol.14 (5), p.94-94, Article 94</ispartof><rights>Copyright: © Sandström et al.</rights><rights>COPYRIGHT 2021 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2021</rights><rights>Copyright: © Sandström et al. 2021</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c558t-99ea06a21e2a3c978ed23d83af1e36db1b00b8ff32bf322b706d7b46f63c1aa13</citedby><orcidid>0000-0002-3026-1901</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976380/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976380/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33767863$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-174638$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:233767863$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Sandström, Josefine</creatorcontrib><creatorcontrib>Balian, Alien</creatorcontrib><creatorcontrib>Lockowandt, Rebecca</creatorcontrib><creatorcontrib>Fornander, Tommy</creatorcontrib><creatorcontrib>Nordenskjöld, Bo</creatorcontrib><creatorcontrib>Lindström, Linda</creatorcontrib><creatorcontrib>Pérez-Tenorio, Gizeh</creatorcontrib><creatorcontrib>Stål, Olle</creatorcontrib><title>IP6K2 predicts favorable clinical outcome of primary breast cancer</title><title>Molecular and clinical oncology</title><addtitle>Mol Clin Oncol</addtitle><description>The inositol hexakisphosphate kinase (
) 1 and 2 genes are localized at 3p21.31, a highly altered gene-dense chromosomal region in cancer. The IP6Ks convert IP6 to IP7, which inhibits activation of the tumor-promoting PI3K/Akt/mTOR signaling pathway. IP6K2 has been suggested to be involved in p53-induced apoptosis, while IP6K1 may stimulate tumor growth and migration. The present study aimed to elucidate the role of the two IP6Ks in predicting outcome in patients with breast cancer. To the best of our knowledge, the role of IP6K was analyzed for the first time in tumors from three cohorts of patients with breast cancer; one Swedish low-risk cohort, one Dutch cohort and the TCGA dataset. Analyses of gene -and protein expression and subcellular localization were included. IP6K2 gene expression was associated with ER positivity and nuclear p-Akt. Improved prognosis was detected with high IP6K2 gene expression compared with low IP6K2 gene expression in systemically untreated patients in the Swedish low-risk and Dutch cohorts. In the TCGA dataset, IP6K2 prognostic value was significant when selecting for tumors with wild-type
. A multivariable analysis testing IP6K2 against other cancer-related genes at 3p.21.31, including IP6K1 and clinical biomarkers, revealed that IP6K2 was associated with decreased risk of distant recurrence. IP6K1 was associated with increased risk of distant recurrence in the multivariable test and protein analysis revealed trends of worse prognosis with high IP6K1 in the cytoplasm. The expression levels of IP6K1 and IP6K2 were associated to a high extent; however, a diverging prognostic value of the two genes was observed in breast cancer. The present data suggest that IP6K2 can be a favorable prognostic factor, while IP6K1 may not be.</description><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Care and treatment</subject><subject>Clinical outcomes</subject><subject>Ethnicity</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomics</subject><subject>Inositol</subject><subject>Kinases</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Oncology</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Software</subject><subject>Tumor proteins</subject><subject>Tumors</subject><issn>2049-9450</issn><issn>2049-9469</issn><issn>2049-9469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><sourceid>D8T</sourceid><recordid>eNp9kstv1DAQxi0EotXSI1cUiQuXLH4kflyQlpZHRSU4AFfLccaLixMXOyniv8dRw8IihC3Lo_HvG9ujD6HHBG-ZVPT5YOOWYkq2lLb8HjqluFG1ari6f4hbfILOcr7GZSiBaaseohPGBBeSs1P08vIDf0ermwS9t1OunLmNyXQBKhv86K0JVZwnGweooiuYH0z6UXUJTJ4qa0YL6RF64EzIcLbuG_Tp9auP52_rq_dvLs93V7VtWznVSoHB3FAC1DCrhISesl4y4wgw3nekw7iTzjHalUU7gXkvuoY7ziwxhrANqu_q5u9wM3d6fYyOxus19bVEoBvOqJL_5S_8552Oaa-DnzURRbHwL-74Ag_QWxinZMKR7Phk9F_0Pt5qoUTR41Lg2VogxW8z5EkPPlsIwYwQ56xpizmVjJbGb9DTv9DrOKextG-hhJRcUfmb2psA2o8ulnvtUlTveCtUS1jTFGr7D6rMHgZv4wjOl_yRYG2MTTHnBO7wR4L14itdfKUXX-nFV4V_8mdjDvQvF7Gf0s7H4Q</recordid><startdate>20210501</startdate><enddate>20210501</enddate><creator>Sandström, Josefine</creator><creator>Balian, Alien</creator><creator>Lockowandt, Rebecca</creator><creator>Fornander, Tommy</creator><creator>Nordenskjöld, Bo</creator><creator>Lindström, Linda</creator><creator>Pérez-Tenorio, Gizeh</creator><creator>Stål, Olle</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><general>D.A. Spandidos</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>ABXSW</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>DG8</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-3026-1901</orcidid></search><sort><creationdate>20210501</creationdate><title>IP6K2 predicts favorable clinical outcome of primary breast cancer</title><author>Sandström, Josefine ; Balian, Alien ; Lockowandt, Rebecca ; Fornander, Tommy ; Nordenskjöld, Bo ; Lindström, Linda ; Pérez-Tenorio, Gizeh ; Stål, Olle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c558t-99ea06a21e2a3c978ed23d83af1e36db1b00b8ff32bf322b706d7b46f63c1aa13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cancer patients</topic><topic>Care and treatment</topic><topic>Clinical outcomes</topic><topic>Ethnicity</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomics</topic><topic>Inositol</topic><topic>Kinases</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Oncology</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Software</topic><topic>Tumor proteins</topic><topic>Tumors</topic><toplevel>online_resources</toplevel><creatorcontrib>Sandström, Josefine</creatorcontrib><creatorcontrib>Balian, Alien</creatorcontrib><creatorcontrib>Lockowandt, Rebecca</creatorcontrib><creatorcontrib>Fornander, Tommy</creatorcontrib><creatorcontrib>Nordenskjöld, Bo</creatorcontrib><creatorcontrib>Lindström, Linda</creatorcontrib><creatorcontrib>Pérez-Tenorio, Gizeh</creatorcontrib><creatorcontrib>Stål, Olle</creatorcontrib><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>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>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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><collection>PubMed Central (Full Participant titles)</collection><collection>SWEPUB Linköpings universitet full text</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Linköpings universitet</collection><collection>SwePub Articles full text</collection><jtitle>Molecular and clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sandström, Josefine</au><au>Balian, Alien</au><au>Lockowandt, Rebecca</au><au>Fornander, Tommy</au><au>Nordenskjöld, Bo</au><au>Lindström, Linda</au><au>Pérez-Tenorio, Gizeh</au><au>Stål, Olle</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IP6K2 predicts favorable clinical outcome of primary breast cancer</atitle><jtitle>Molecular and clinical oncology</jtitle><addtitle>Mol Clin Oncol</addtitle><date>2021-05-01</date><risdate>2021</risdate><volume>14</volume><issue>5</issue><spage>94</spage><epage>94</epage><pages>94-94</pages><artnum>94</artnum><issn>2049-9450</issn><issn>2049-9469</issn><eissn>2049-9469</eissn><abstract>The inositol hexakisphosphate kinase (
) 1 and 2 genes are localized at 3p21.31, a highly altered gene-dense chromosomal region in cancer. The IP6Ks convert IP6 to IP7, which inhibits activation of the tumor-promoting PI3K/Akt/mTOR signaling pathway. IP6K2 has been suggested to be involved in p53-induced apoptosis, while IP6K1 may stimulate tumor growth and migration. The present study aimed to elucidate the role of the two IP6Ks in predicting outcome in patients with breast cancer. To the best of our knowledge, the role of IP6K was analyzed for the first time in tumors from three cohorts of patients with breast cancer; one Swedish low-risk cohort, one Dutch cohort and the TCGA dataset. Analyses of gene -and protein expression and subcellular localization were included. IP6K2 gene expression was associated with ER positivity and nuclear p-Akt. Improved prognosis was detected with high IP6K2 gene expression compared with low IP6K2 gene expression in systemically untreated patients in the Swedish low-risk and Dutch cohorts. In the TCGA dataset, IP6K2 prognostic value was significant when selecting for tumors with wild-type
. A multivariable analysis testing IP6K2 against other cancer-related genes at 3p.21.31, including IP6K1 and clinical biomarkers, revealed that IP6K2 was associated with decreased risk of distant recurrence. IP6K1 was associated with increased risk of distant recurrence in the multivariable test and protein analysis revealed trends of worse prognosis with high IP6K1 in the cytoplasm. The expression levels of IP6K1 and IP6K2 were associated to a high extent; however, a diverging prognostic value of the two genes was observed in breast cancer. The present data suggest that IP6K2 can be a favorable prognostic factor, while IP6K1 may not be.</abstract><cop>England</cop><pub>Spandidos Publications</pub><pmid>33767863</pmid><doi>10.3892/mco.2021.2256</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-3026-1901</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2049-9450 |
| ispartof | Molecular and clinical oncology, 2021-05, Vol.14 (5), p.94-94, Article 94 |
| issn | 2049-9450 2049-9469 2049-9469 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_463298 |
| source | Spandidos Publications Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; SWEPUB Freely available online |
| subjects | Antibodies Apoptosis Breast cancer Cancer Cancer patients Care and treatment Clinical outcomes Ethnicity Gene expression Genes Genetic aspects Genomics Inositol Kinases Medical prognosis Medical research Medicine, Experimental Oncology Patient outcomes Patients Prognosis Protein expression Proteins Software Tumor proteins Tumors |
| title | IP6K2 predicts favorable clinical outcome of primary breast cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T06%3A31%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=IP6K2%20predicts%20favorable%20clinical%20outcome%20of%20primary%20breast%20cancer&rft.jtitle=Molecular%20and%20clinical%20oncology&rft.au=Sandstr%C3%B6m,%20Josefine&rft.date=2021-05-01&rft.volume=14&rft.issue=5&rft.spage=94&rft.epage=94&rft.pages=94-94&rft.artnum=94&rft.issn=2049-9450&rft.eissn=2049-9469&rft_id=info:doi/10.3892/mco.2021.2256&rft_dat=%3Cgale_swepu%3EA657951344%3C/gale_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2507886928&rft_id=info:pmid/33767863&rft_galeid=A657951344&rfr_iscdi=true |