ZNF677 downregulation by promoter hypermethylation as a driver event through gastric tumorigenesis
Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide, due to poor prognosis and treatment failure; demanding new diagnostic and therapeutic targets. Therefore, in the present study, the methylation and expression status of ZNF677, as a promising tumor suppressor, were i...
Gespeichert in:
| Veröffentlicht in: | Experimental and molecular pathology 2021-08, Vol.121, p.104663-104663, Article 104663 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 104663 |
|---|---|
| container_issue | |
| container_start_page | 104663 |
| container_title | Experimental and molecular pathology |
| container_volume | 121 |
| creator | Bidar, Negar Rezaei, Tayebeh Amini, Mohammad Jebelli, Asiyeh Mokhtarzadeh, Ahad Baradaran, Behzad |
| description | Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide, due to poor prognosis and treatment failure; demanding new diagnostic and therapeutic targets. Therefore, in the present study, the methylation and expression status of ZNF677, as a promising tumor suppressor, were investigated in GC. Gene Expression Omnibus (GEO) datasets were used to initially evaluate ZNF677 expression and methylation in GC samples. Confirmation was performed on fifty internal samples, including gastric tumors and adjacent normal specimens, using q-MSP and q-PCR methods. Further validations were done using The Cancer Genome Atlas (TCGA) data on human cancers. The obtained results in silico and experimentally illustrated that ZNF677 is significantly hypermethylated and downregulated through gastric tumorigenesis. ZNF677 methylation levels were also correlated with perineural invasion (p = 0.0382) in internal samples. Furthermore, Spearman's correlation analysis showed that ZNF677 methylation is negatively (r = −0.4614, p |
| doi_str_mv | 10.1016/j.yexmp.2021.104663 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2545594622</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014480021000629</els_id><sourcerecordid>2545594622</sourcerecordid><originalsourceid>FETCH-LOGICAL-c336t-58d871e16bf2a822a99df5e405b369529270bd56bdf0676b0d64bbd0dd61bcda3</originalsourceid><addsrcrecordid>eNp9kD9PwzAQxS0EEqXwCVg8sqScndhpBgZU8U9CsMDCYtnxpXXVxMV2Cvn2BNqZ6aR7753u_Qi5ZDBjwOT1ejbgd7udceBs3BRS5kdkwqCSGVSFOCYTAFZkxRzglJzFuAaAChifEPPxci_Lklr_1QVc9hudnO-oGeg2-NYnDHQ1bDG0mFbDQdSRamqD240i7rBLNK2C75crutQxBVfT1Lc-uCV2GF08JyeN3kS8OMwpeb-_e1s8Zs-vD0-L2-esznOZMjG385Ihk6bhes65rirbCCxAmFxWgle8BGOFNLYBWUoDVhbGWLBWMlNbnU_J1f7u-PlnjzGp1sUaNxvdoe-j4qIQoiok56M131vr4GMM2KhtcK0Og2Kgfomqtfojqn6Jqj3RMXWzT-HYYucwqFg77Gq0LmCdlPXu3_wPdQWCSw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2545594622</pqid></control><display><type>article</type><title>ZNF677 downregulation by promoter hypermethylation as a driver event through gastric tumorigenesis</title><source>Elsevier ScienceDirect Journals Complete - AutoHoldings</source><creator>Bidar, Negar ; Rezaei, Tayebeh ; Amini, Mohammad ; Jebelli, Asiyeh ; Mokhtarzadeh, Ahad ; Baradaran, Behzad</creator><creatorcontrib>Bidar, Negar ; Rezaei, Tayebeh ; Amini, Mohammad ; Jebelli, Asiyeh ; Mokhtarzadeh, Ahad ; Baradaran, Behzad</creatorcontrib><description>Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide, due to poor prognosis and treatment failure; demanding new diagnostic and therapeutic targets. Therefore, in the present study, the methylation and expression status of ZNF677, as a promising tumor suppressor, were investigated in GC. Gene Expression Omnibus (GEO) datasets were used to initially evaluate ZNF677 expression and methylation in GC samples. Confirmation was performed on fifty internal samples, including gastric tumors and adjacent normal specimens, using q-MSP and q-PCR methods. Further validations were done using The Cancer Genome Atlas (TCGA) data on human cancers. The obtained results in silico and experimentally illustrated that ZNF677 is significantly hypermethylated and downregulated through gastric tumorigenesis. ZNF677 methylation levels were also correlated with perineural invasion (p = 0.0382) in internal samples. Furthermore, Spearman's correlation analysis showed that ZNF677 methylation is negatively (r = −0.4614, p < 0.0001) correlated with its mRNA expression levels. ROC curve analysis also illustrated the high diagnostic value of ZNF677 methylation for early detection of GC (AUC = 0.8592). Gene set enrichment analysis further revealed that ZNF677 participates in the regulation of cellular processes such as cell proliferation in GC. Moreover, in addition to hypermethylation in other malignancies, including breast, lung, and colorectal cancers, ZNF677 was hypermethylated in precancerous gastric tissues with intestinal metaplasia, indicating its methylation as a driver event through tumorigenesis. Taken together, our results suggest ZNF677 as a potential tumor suppressor gene, which could be considered as a diagnostic and therapeutic target for GC.</description><identifier>ISSN: 0014-4800</identifier><identifier>EISSN: 1096-0945</identifier><identifier>DOI: 10.1016/j.yexmp.2021.104663</identifier><language>eng</language><publisher>Elsevier Inc</publisher><subject>Biomarker ; DNA methylation ; Gastric cancer ; GEO ; TCGA ; ZNF677</subject><ispartof>Experimental and molecular pathology, 2021-08, Vol.121, p.104663-104663, Article 104663</ispartof><rights>2021 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c336t-58d871e16bf2a822a99df5e405b369529270bd56bdf0676b0d64bbd0dd61bcda3</citedby><cites>FETCH-LOGICAL-c336t-58d871e16bf2a822a99df5e405b369529270bd56bdf0676b0d64bbd0dd61bcda3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.yexmp.2021.104663$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids></links><search><creatorcontrib>Bidar, Negar</creatorcontrib><creatorcontrib>Rezaei, Tayebeh</creatorcontrib><creatorcontrib>Amini, Mohammad</creatorcontrib><creatorcontrib>Jebelli, Asiyeh</creatorcontrib><creatorcontrib>Mokhtarzadeh, Ahad</creatorcontrib><creatorcontrib>Baradaran, Behzad</creatorcontrib><title>ZNF677 downregulation by promoter hypermethylation as a driver event through gastric tumorigenesis</title><title>Experimental and molecular pathology</title><description>Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide, due to poor prognosis and treatment failure; demanding new diagnostic and therapeutic targets. Therefore, in the present study, the methylation and expression status of ZNF677, as a promising tumor suppressor, were investigated in GC. Gene Expression Omnibus (GEO) datasets were used to initially evaluate ZNF677 expression and methylation in GC samples. Confirmation was performed on fifty internal samples, including gastric tumors and adjacent normal specimens, using q-MSP and q-PCR methods. Further validations were done using The Cancer Genome Atlas (TCGA) data on human cancers. The obtained results in silico and experimentally illustrated that ZNF677 is significantly hypermethylated and downregulated through gastric tumorigenesis. ZNF677 methylation levels were also correlated with perineural invasion (p = 0.0382) in internal samples. Furthermore, Spearman's correlation analysis showed that ZNF677 methylation is negatively (r = −0.4614, p < 0.0001) correlated with its mRNA expression levels. ROC curve analysis also illustrated the high diagnostic value of ZNF677 methylation for early detection of GC (AUC = 0.8592). Gene set enrichment analysis further revealed that ZNF677 participates in the regulation of cellular processes such as cell proliferation in GC. Moreover, in addition to hypermethylation in other malignancies, including breast, lung, and colorectal cancers, ZNF677 was hypermethylated in precancerous gastric tissues with intestinal metaplasia, indicating its methylation as a driver event through tumorigenesis. Taken together, our results suggest ZNF677 as a potential tumor suppressor gene, which could be considered as a diagnostic and therapeutic target for GC.</description><subject>Biomarker</subject><subject>DNA methylation</subject><subject>Gastric cancer</subject><subject>GEO</subject><subject>TCGA</subject><subject>ZNF677</subject><issn>0014-4800</issn><issn>1096-0945</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kD9PwzAQxS0EEqXwCVg8sqScndhpBgZU8U9CsMDCYtnxpXXVxMV2Cvn2BNqZ6aR7753u_Qi5ZDBjwOT1ejbgd7udceBs3BRS5kdkwqCSGVSFOCYTAFZkxRzglJzFuAaAChifEPPxci_Lklr_1QVc9hudnO-oGeg2-NYnDHQ1bDG0mFbDQdSRamqD240i7rBLNK2C75crutQxBVfT1Lc-uCV2GF08JyeN3kS8OMwpeb-_e1s8Zs-vD0-L2-esznOZMjG385Ihk6bhes65rirbCCxAmFxWgle8BGOFNLYBWUoDVhbGWLBWMlNbnU_J1f7u-PlnjzGp1sUaNxvdoe-j4qIQoiok56M131vr4GMM2KhtcK0Og2Kgfomqtfojqn6Jqj3RMXWzT-HYYucwqFg77Gq0LmCdlPXu3_wPdQWCSw</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Bidar, Negar</creator><creator>Rezaei, Tayebeh</creator><creator>Amini, Mohammad</creator><creator>Jebelli, Asiyeh</creator><creator>Mokhtarzadeh, Ahad</creator><creator>Baradaran, Behzad</creator><general>Elsevier Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202108</creationdate><title>ZNF677 downregulation by promoter hypermethylation as a driver event through gastric tumorigenesis</title><author>Bidar, Negar ; Rezaei, Tayebeh ; Amini, Mohammad ; Jebelli, Asiyeh ; Mokhtarzadeh, Ahad ; Baradaran, Behzad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c336t-58d871e16bf2a822a99df5e405b369529270bd56bdf0676b0d64bbd0dd61bcda3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biomarker</topic><topic>DNA methylation</topic><topic>Gastric cancer</topic><topic>GEO</topic><topic>TCGA</topic><topic>ZNF677</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bidar, Negar</creatorcontrib><creatorcontrib>Rezaei, Tayebeh</creatorcontrib><creatorcontrib>Amini, Mohammad</creatorcontrib><creatorcontrib>Jebelli, Asiyeh</creatorcontrib><creatorcontrib>Mokhtarzadeh, Ahad</creatorcontrib><creatorcontrib>Baradaran, Behzad</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental and molecular pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bidar, Negar</au><au>Rezaei, Tayebeh</au><au>Amini, Mohammad</au><au>Jebelli, Asiyeh</au><au>Mokhtarzadeh, Ahad</au><au>Baradaran, Behzad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ZNF677 downregulation by promoter hypermethylation as a driver event through gastric tumorigenesis</atitle><jtitle>Experimental and molecular pathology</jtitle><date>2021-08</date><risdate>2021</risdate><volume>121</volume><spage>104663</spage><epage>104663</epage><pages>104663-104663</pages><artnum>104663</artnum><issn>0014-4800</issn><eissn>1096-0945</eissn><abstract>Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide, due to poor prognosis and treatment failure; demanding new diagnostic and therapeutic targets. Therefore, in the present study, the methylation and expression status of ZNF677, as a promising tumor suppressor, were investigated in GC. Gene Expression Omnibus (GEO) datasets were used to initially evaluate ZNF677 expression and methylation in GC samples. Confirmation was performed on fifty internal samples, including gastric tumors and adjacent normal specimens, using q-MSP and q-PCR methods. Further validations were done using The Cancer Genome Atlas (TCGA) data on human cancers. The obtained results in silico and experimentally illustrated that ZNF677 is significantly hypermethylated and downregulated through gastric tumorigenesis. ZNF677 methylation levels were also correlated with perineural invasion (p = 0.0382) in internal samples. Furthermore, Spearman's correlation analysis showed that ZNF677 methylation is negatively (r = −0.4614, p < 0.0001) correlated with its mRNA expression levels. ROC curve analysis also illustrated the high diagnostic value of ZNF677 methylation for early detection of GC (AUC = 0.8592). Gene set enrichment analysis further revealed that ZNF677 participates in the regulation of cellular processes such as cell proliferation in GC. Moreover, in addition to hypermethylation in other malignancies, including breast, lung, and colorectal cancers, ZNF677 was hypermethylated in precancerous gastric tissues with intestinal metaplasia, indicating its methylation as a driver event through tumorigenesis. Taken together, our results suggest ZNF677 as a potential tumor suppressor gene, which could be considered as a diagnostic and therapeutic target for GC.</abstract><pub>Elsevier Inc</pub><doi>10.1016/j.yexmp.2021.104663</doi><tpages>1</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-4800 |
| ispartof | Experimental and molecular pathology, 2021-08, Vol.121, p.104663-104663, Article 104663 |
| issn | 0014-4800 1096-0945 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2545594622 |
| source | Elsevier ScienceDirect Journals Complete - AutoHoldings |
| subjects | Biomarker DNA methylation Gastric cancer GEO TCGA ZNF677 |
| title | ZNF677 downregulation by promoter hypermethylation as a driver event through gastric tumorigenesis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T09%3A31%3A30IST&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=ZNF677%20downregulation%20by%20promoter%20hypermethylation%20as%20a%20driver%20event%20through%20gastric%20tumorigenesis&rft.jtitle=Experimental%20and%20molecular%20pathology&rft.au=Bidar,%20Negar&rft.date=2021-08&rft.volume=121&rft.spage=104663&rft.epage=104663&rft.pages=104663-104663&rft.artnum=104663&rft.issn=0014-4800&rft.eissn=1096-0945&rft_id=info:doi/10.1016/j.yexmp.2021.104663&rft_dat=%3Cproquest_cross%3E2545594622%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=2545594622&rft_id=info:pmid/&rft_els_id=S0014480021000629&rfr_iscdi=true |