Alpha-enolase is a potential prognostic marker in clear cell renal cell carcinoma
Clear cell renal cell carcinoma (ccRCC) is an aggressive disease with unpredictable behaviour. Clinical parameters are not always accurate for prognosis prediction. The integration of molecular markers to prognostic models can significantly improve prognostic assessment and consequently patient mana...
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| Veröffentlicht in: | Clinical & experimental metastasis 2015-08, Vol.32 (6), p.531-541 |
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| creator | White-Al Habeeb, Nicole M. Di Meo, Ashley Scorilas, Andreas Rotondo, Fabio Masui, Olena Seivwright, Annetta Gabril, Manal Girgis, Andrew H. A. Jewett, Michael A. Yousef, George M. |
| description | Clear cell renal cell carcinoma (ccRCC) is an aggressive disease with unpredictable behaviour. Clinical parameters are not always accurate for prognosis prediction. The integration of molecular markers to prognostic models can significantly improve prognostic assessment and consequently patient management. We assessed the expression of alpha-enolase (ENO1) protein by immunohistochemistry in 360 patients with primary ccRCC and correlated its expression with multiple clinicopathological parameters including stage, grade, tumor size, disease-free and overall survival. Cox proportional hazard regression models adjusted for clinicopathological factors were used to test for a link between ENO1 expression and both disease-free and overall survival. We correlated ENO1 mRNA expression with overall survival in an independent set of 428 ccRCC cases from The Cancer Genome Atlas. ENO1 showed cytoplasmic, membranous and nuclear staining patterns. There is a statistically significant negative correlation between ENO1 expression, tumor stage, and grade. ENO1 expression also shows a statistically significant direct correlation with disease-free survival (
p
= 0.011) and overall survival (
p
= 0.030) in ccRCC. Patients with higher ENO1 expression had lower hazard ratio of recurrence, although this was not statistically significant (HR = 0.330,
p
= 0.060). These findings were validated at the mRNA level in an independent set of 428 ccRCC cases which also showed that low ENO1 expression is associated with significantly shorter overall survival. Down-regulation of ENO1 can be a predictor of poor prognosis in ccRCC, and it can be a potential prognostic marker. |
| doi_str_mv | 10.1007/s10585-015-9725-2 |
| format | Article |
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p
= 0.011) and overall survival (
p
= 0.030) in ccRCC. Patients with higher ENO1 expression had lower hazard ratio of recurrence, although this was not statistically significant (HR = 0.330,
p
= 0.060). These findings were validated at the mRNA level in an independent set of 428 ccRCC cases which also showed that low ENO1 expression is associated with significantly shorter overall survival. Down-regulation of ENO1 can be a predictor of poor prognosis in ccRCC, and it can be a potential prognostic marker.</description><identifier>ISSN: 0262-0898</identifier><identifier>EISSN: 1573-7276</identifier><identifier>DOI: 10.1007/s10585-015-9725-2</identifier><identifier>PMID: 26037892</identifier><identifier>CODEN: CEXMD2</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Renal Cell - genetics ; Carcinoma, Renal Cell - metabolism ; Carcinoma, Renal Cell - mortality ; Carcinoma, Renal Cell - pathology ; Cohort Studies ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Follow-Up Studies ; Hematology ; Humans ; Immunoenzyme Techniques ; Kidney Neoplasms - genetics ; Kidney Neoplasms - metabolism ; Kidney Neoplasms - mortality ; Kidney Neoplasms - pathology ; MicroRNAs - genetics ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - metabolism ; Neoplasm Recurrence, Local - mortality ; Neoplasm Recurrence, Local - pathology ; Neoplasm Staging ; Oncology ; Phosphopyruvate Hydratase - genetics ; Phosphopyruvate Hydratase - metabolism ; Prognosis ; Real-Time Polymerase Chain Reaction ; Research Paper ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Surgical Oncology ; Survival Rate ; Tumor Cells, Cultured ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism</subject><ispartof>Clinical & experimental metastasis, 2015-08, Vol.32 (6), p.531-541</ispartof><rights>Springer Science+Business Media Dordrecht 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-3a12f9f96579de3ef725a2a1d5fed4cfe54b40e74e156fe6f96e642cffb4a1a83</citedby><cites>FETCH-LOGICAL-c442t-3a12f9f96579de3ef725a2a1d5fed4cfe54b40e74e156fe6f96e642cffb4a1a83</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/s10585-015-9725-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10585-015-9725-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26037892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>White-Al Habeeb, Nicole M.</creatorcontrib><creatorcontrib>Di Meo, Ashley</creatorcontrib><creatorcontrib>Scorilas, Andreas</creatorcontrib><creatorcontrib>Rotondo, Fabio</creatorcontrib><creatorcontrib>Masui, Olena</creatorcontrib><creatorcontrib>Seivwright, Annetta</creatorcontrib><creatorcontrib>Gabril, Manal</creatorcontrib><creatorcontrib>Girgis, Andrew H. A.</creatorcontrib><creatorcontrib>Jewett, Michael A.</creatorcontrib><creatorcontrib>Yousef, George M.</creatorcontrib><title>Alpha-enolase is a potential prognostic marker in clear cell renal cell carcinoma</title><title>Clinical & experimental metastasis</title><addtitle>Clin Exp Metastasis</addtitle><addtitle>Clin Exp Metastasis</addtitle><description>Clear cell renal cell carcinoma (ccRCC) is an aggressive disease with unpredictable behaviour. Clinical parameters are not always accurate for prognosis prediction. The integration of molecular markers to prognostic models can significantly improve prognostic assessment and consequently patient management. We assessed the expression of alpha-enolase (ENO1) protein by immunohistochemistry in 360 patients with primary ccRCC and correlated its expression with multiple clinicopathological parameters including stage, grade, tumor size, disease-free and overall survival. Cox proportional hazard regression models adjusted for clinicopathological factors were used to test for a link between ENO1 expression and both disease-free and overall survival. We correlated ENO1 mRNA expression with overall survival in an independent set of 428 ccRCC cases from The Cancer Genome Atlas. ENO1 showed cytoplasmic, membranous and nuclear staining patterns. There is a statistically significant negative correlation between ENO1 expression, tumor stage, and grade. ENO1 expression also shows a statistically significant direct correlation with disease-free survival (
p
= 0.011) and overall survival (
p
= 0.030) in ccRCC. Patients with higher ENO1 expression had lower hazard ratio of recurrence, although this was not statistically significant (HR = 0.330,
p
= 0.060). These findings were validated at the mRNA level in an independent set of 428 ccRCC cases which also showed that low ENO1 expression is associated with significantly shorter overall survival. Down-regulation of ENO1 can be a predictor of poor prognosis in ccRCC, and it can be a potential prognostic marker.</description><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Renal Cell - genetics</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Carcinoma, Renal Cell - mortality</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Cohort Studies</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Follow-Up Studies</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Kidney Neoplasms - genetics</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Kidney Neoplasms - mortality</subject><subject>Kidney Neoplasms - pathology</subject><subject>MicroRNAs - genetics</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - metabolism</subject><subject>Neoplasm Recurrence, Local - mortality</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Phosphopyruvate Hydratase - genetics</subject><subject>Phosphopyruvate Hydratase - metabolism</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Research Paper</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Surgical Oncology</subject><subject>Survival Rate</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><issn>0262-0898</issn><issn>1573-7276</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</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>eNp1kMtKAzEUhoMotlYfwI0E3LiJJplcZpaleIOCCLoOaeakTp1LTWYWvr3pRRHBVQL5zp__fAidM3rNKNU3kVGZS0KZJIXmkvADNGZSZ0RzrQ7RmHLFCc2LfIROYlxRSoXW-TEacUUznRd8jJ6n9frNEmi72kbAVcQWr7se2r6yNV6Hbtl2sa8cbmx4h4CrFrsabMAO6hoHaBO1vTobXNV2jT1FR97WEc725wS93t2-zB7I_On-cTadEycE70lmGfeFL5TURQkZ-LSA5ZaV0kMpnAcpFoKCFsCk8qASCUpw5_1CWGbzbIKudrmp5McAsTdNFTdVbAvdEA1TyQnjmhYJvfyDrrohpOpbSimudLEJZDvKhS7GAN6sQ5XW_jSMmo1vs_Ntkm-z8W14mrnYJw-LBsqfiW_BCeA7IKandgnh19f_pn4BAsyK6Q</recordid><startdate>20150801</startdate><enddate>20150801</enddate><creator>White-Al Habeeb, Nicole M.</creator><creator>Di Meo, Ashley</creator><creator>Scorilas, Andreas</creator><creator>Rotondo, Fabio</creator><creator>Masui, Olena</creator><creator>Seivwright, Annetta</creator><creator>Gabril, Manal</creator><creator>Girgis, Andrew H. A.</creator><creator>Jewett, Michael A.</creator><creator>Yousef, George M.</creator><general>Springer Netherlands</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>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FG</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20150801</creationdate><title>Alpha-enolase is a potential prognostic marker in clear cell renal cell carcinoma</title><author>White-Al Habeeb, Nicole M. ; Di Meo, Ashley ; Scorilas, Andreas ; Rotondo, Fabio ; Masui, Olena ; Seivwright, Annetta ; Gabril, Manal ; Girgis, Andrew H. A. ; Jewett, Michael A. ; Yousef, George M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-3a12f9f96579de3ef725a2a1d5fed4cfe54b40e74e156fe6f96e642cffb4a1a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Renal Cell - genetics</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>Carcinoma, Renal Cell - mortality</topic><topic>Carcinoma, Renal Cell - pathology</topic><topic>Cohort Studies</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Follow-Up Studies</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Kidney Neoplasms - genetics</topic><topic>Kidney Neoplasms - metabolism</topic><topic>Kidney Neoplasms - mortality</topic><topic>Kidney Neoplasms - pathology</topic><topic>MicroRNAs - genetics</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Neoplasm Recurrence, Local - metabolism</topic><topic>Neoplasm Recurrence, Local - mortality</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Phosphopyruvate Hydratase - genetics</topic><topic>Phosphopyruvate Hydratase - metabolism</topic><topic>Prognosis</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Research Paper</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Surgical Oncology</topic><topic>Survival Rate</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>White-Al Habeeb, Nicole M.</creatorcontrib><creatorcontrib>Di Meo, Ashley</creatorcontrib><creatorcontrib>Scorilas, Andreas</creatorcontrib><creatorcontrib>Rotondo, Fabio</creatorcontrib><creatorcontrib>Masui, Olena</creatorcontrib><creatorcontrib>Seivwright, Annetta</creatorcontrib><creatorcontrib>Gabril, Manal</creatorcontrib><creatorcontrib>Girgis, Andrew H. A.</creatorcontrib><creatorcontrib>Jewett, Michael A.</creatorcontrib><creatorcontrib>Yousef, George M.</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>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Technology 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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical & experimental metastasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>White-Al Habeeb, Nicole M.</au><au>Di Meo, Ashley</au><au>Scorilas, Andreas</au><au>Rotondo, Fabio</au><au>Masui, Olena</au><au>Seivwright, Annetta</au><au>Gabril, Manal</au><au>Girgis, Andrew H. A.</au><au>Jewett, Michael A.</au><au>Yousef, George M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alpha-enolase is a potential prognostic marker in clear cell renal cell carcinoma</atitle><jtitle>Clinical & experimental metastasis</jtitle><stitle>Clin Exp Metastasis</stitle><addtitle>Clin Exp Metastasis</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>32</volume><issue>6</issue><spage>531</spage><epage>541</epage><pages>531-541</pages><issn>0262-0898</issn><eissn>1573-7276</eissn><coden>CEXMD2</coden><abstract>Clear cell renal cell carcinoma (ccRCC) is an aggressive disease with unpredictable behaviour. Clinical parameters are not always accurate for prognosis prediction. The integration of molecular markers to prognostic models can significantly improve prognostic assessment and consequently patient management. We assessed the expression of alpha-enolase (ENO1) protein by immunohistochemistry in 360 patients with primary ccRCC and correlated its expression with multiple clinicopathological parameters including stage, grade, tumor size, disease-free and overall survival. Cox proportional hazard regression models adjusted for clinicopathological factors were used to test for a link between ENO1 expression and both disease-free and overall survival. We correlated ENO1 mRNA expression with overall survival in an independent set of 428 ccRCC cases from The Cancer Genome Atlas. ENO1 showed cytoplasmic, membranous and nuclear staining patterns. There is a statistically significant negative correlation between ENO1 expression, tumor stage, and grade. ENO1 expression also shows a statistically significant direct correlation with disease-free survival (
p
= 0.011) and overall survival (
p
= 0.030) in ccRCC. Patients with higher ENO1 expression had lower hazard ratio of recurrence, although this was not statistically significant (HR = 0.330,
p
= 0.060). These findings were validated at the mRNA level in an independent set of 428 ccRCC cases which also showed that low ENO1 expression is associated with significantly shorter overall survival. Down-regulation of ENO1 can be a predictor of poor prognosis in ccRCC, and it can be a potential prognostic marker.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>26037892</pmid><doi>10.1007/s10585-015-9725-2</doi><tpages>11</tpages></addata></record> |
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| subjects | Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - mortality Carcinoma, Renal Cell - pathology Cohort Studies DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Follow-Up Studies Hematology Humans Immunoenzyme Techniques Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kidney Neoplasms - mortality Kidney Neoplasms - pathology MicroRNAs - genetics Neoplasm Grading Neoplasm Invasiveness Neoplasm Recurrence, Local - genetics Neoplasm Recurrence, Local - metabolism Neoplasm Recurrence, Local - mortality Neoplasm Recurrence, Local - pathology Neoplasm Staging Oncology Phosphopyruvate Hydratase - genetics Phosphopyruvate Hydratase - metabolism Prognosis Real-Time Polymerase Chain Reaction Research Paper Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Surgical Oncology Survival Rate Tumor Cells, Cultured Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism |
| title | Alpha-enolase is a potential prognostic marker in clear cell renal cell carcinoma |
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