Noxa upregulation and 5‐gene apoptotic biomarker panel in colorectal cancer
Background NOXA and MCL1 are involved in the intrinsic pathway of apoptosis, where Noxa selectively binds to MCL1 and prevents it from inhibiting apoptosis. Both factors are considered as potential tumour biomarkers, while MCL1 has attracted interest as target in cancer. The purpose of this study wa...
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| Veröffentlicht in: | European journal of clinical investigation 2021-01, Vol.51 (1), p.e13353-n/a |
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| creator | Kosmidou, Vivian Vlassi, Margarita Anagiotos, Kyriakos Raftopoulou, Sofia Kalogerakou, Eirini Skarmalioraki, Salomi Aggeli, Chrysanthi Choreftaki, Theodosia Zografos, George Pintzas, Alexander |
| description | Background
NOXA and MCL1 are involved in the intrinsic pathway of apoptosis, where Noxa selectively binds to MCL1 and prevents it from inhibiting apoptosis. Both factors are considered as potential tumour biomarkers, while MCL1 has attracted interest as target in cancer. The purpose of this study was to investigate the expression of NOXA and MCL1 in 160 CRC tumour samples, to investigate their significance, also in combination with IAPs, DR5 expression and KRAS gene mutations in CRC.
Materials and methods
Fresh frozen colorectal tissue was obtained from patients undergoing surgery for CRC. Real‐time quantitative PCR was performed for the determination of mRNA expression levels. Protein expression was determined immunohistochemically. Differences in the mRNA expression profile were evaluated with the nonparametric Wilcoxon signed ranks test. Statistical analysis was performed with the use of Mann‐Whitney U test and receiver‐operating characteristic (ROC) curve.
Results
NOXA was found to be overexpressed in CRC tumours (P |
| doi_str_mv | 10.1111/eci.13353 |
| format | Article |
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NOXA and MCL1 are involved in the intrinsic pathway of apoptosis, where Noxa selectively binds to MCL1 and prevents it from inhibiting apoptosis. Both factors are considered as potential tumour biomarkers, while MCL1 has attracted interest as target in cancer. The purpose of this study was to investigate the expression of NOXA and MCL1 in 160 CRC tumour samples, to investigate their significance, also in combination with IAPs, DR5 expression and KRAS gene mutations in CRC.
Materials and methods
Fresh frozen colorectal tissue was obtained from patients undergoing surgery for CRC. Real‐time quantitative PCR was performed for the determination of mRNA expression levels. Protein expression was determined immunohistochemically. Differences in the mRNA expression profile were evaluated with the nonparametric Wilcoxon signed ranks test. Statistical analysis was performed with the use of Mann‐Whitney U test and receiver‐operating characteristic (ROC) curve.
Results
NOXA was found to be overexpressed in CRC tumours (P < .0001), even from early stage. Moreover, NOXA/MCL1 mRNA expression was significantly elevated in tumour samples compared to normal pairs (P < .0001). ROC curve analysis showed that both NOXA expression and its combination with Mcl1 expression have fair discriminatory value between CRC and normal colorectal tissue. Combinatorial ROC analysis revealed the most significant discriminatory value of NOXA, MCL1 with cIAP1 and cIAP2 (AUC = 0.834, P < .0001) as a 5‐gene panel of markers.
Conclusion
Noxa, Mcl1, DR5, cIAP1 and cIAP2 mRNA expressions are significantly deregulated in CRC and could provide a panel of markers with significant discriminatory value between CRC and normal colorectal tissue.</description><identifier>ISSN: 0014-2972</identifier><identifier>EISSN: 1365-2362</identifier><identifier>DOI: 10.1111/eci.13353</identifier><identifier>PMID: 32682341</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Apoptosis ; Biomarkers ; Cancer ; Colorectal carcinoma ; Combinatorial analysis ; CRC ; Deregulation ; Gene expression ; Mcl-1 protein ; Mutation ; novel 5‐biomarker panel ; Noxa early detection ; Statistical analysis ; Statistical methods ; Surgery ; Tissue analysis ; Tissues ; Tumors</subject><ispartof>European journal of clinical investigation, 2021-01, Vol.51 (1), p.e13353-n/a</ispartof><rights>2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd</rights><rights>2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2021 Stichting European Society for Clinical Investigation Journal Foundation</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2683-66887a537db8d60aedb9f194f33a1045af1c4e98b4c34c37f67b68da605ddf743</citedby><cites>FETCH-LOGICAL-c2683-66887a537db8d60aedb9f194f33a1045af1c4e98b4c34c37f67b68da605ddf743</cites><orcidid>0000-0002-6047-5361</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Feci.13353$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Feci.13353$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32682341$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kosmidou, Vivian</creatorcontrib><creatorcontrib>Vlassi, Margarita</creatorcontrib><creatorcontrib>Anagiotos, Kyriakos</creatorcontrib><creatorcontrib>Raftopoulou, Sofia</creatorcontrib><creatorcontrib>Kalogerakou, Eirini</creatorcontrib><creatorcontrib>Skarmalioraki, Salomi</creatorcontrib><creatorcontrib>Aggeli, Chrysanthi</creatorcontrib><creatorcontrib>Choreftaki, Theodosia</creatorcontrib><creatorcontrib>Zografos, George</creatorcontrib><creatorcontrib>Pintzas, Alexander</creatorcontrib><title>Noxa upregulation and 5‐gene apoptotic biomarker panel in colorectal cancer</title><title>European journal of clinical investigation</title><addtitle>Eur J Clin Invest</addtitle><description>Background
NOXA and MCL1 are involved in the intrinsic pathway of apoptosis, where Noxa selectively binds to MCL1 and prevents it from inhibiting apoptosis. Both factors are considered as potential tumour biomarkers, while MCL1 has attracted interest as target in cancer. The purpose of this study was to investigate the expression of NOXA and MCL1 in 160 CRC tumour samples, to investigate their significance, also in combination with IAPs, DR5 expression and KRAS gene mutations in CRC.
Materials and methods
Fresh frozen colorectal tissue was obtained from patients undergoing surgery for CRC. Real‐time quantitative PCR was performed for the determination of mRNA expression levels. Protein expression was determined immunohistochemically. Differences in the mRNA expression profile were evaluated with the nonparametric Wilcoxon signed ranks test. Statistical analysis was performed with the use of Mann‐Whitney U test and receiver‐operating characteristic (ROC) curve.
Results
NOXA was found to be overexpressed in CRC tumours (P < .0001), even from early stage. Moreover, NOXA/MCL1 mRNA expression was significantly elevated in tumour samples compared to normal pairs (P < .0001). ROC curve analysis showed that both NOXA expression and its combination with Mcl1 expression have fair discriminatory value between CRC and normal colorectal tissue. Combinatorial ROC analysis revealed the most significant discriminatory value of NOXA, MCL1 with cIAP1 and cIAP2 (AUC = 0.834, P < .0001) as a 5‐gene panel of markers.
Conclusion
Noxa, Mcl1, DR5, cIAP1 and cIAP2 mRNA expressions are significantly deregulated in CRC and could provide a panel of markers with significant discriminatory value between CRC and normal colorectal tissue.</description><subject>Apoptosis</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Colorectal carcinoma</subject><subject>Combinatorial analysis</subject><subject>CRC</subject><subject>Deregulation</subject><subject>Gene expression</subject><subject>Mcl-1 protein</subject><subject>Mutation</subject><subject>novel 5‐biomarker panel</subject><subject>Noxa early detection</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Surgery</subject><subject>Tissue analysis</subject><subject>Tissues</subject><subject>Tumors</subject><issn>0014-2972</issn><issn>1365-2362</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp10LtOwzAUBmALgWgpDLwAssQCQ1rfYjsjqgpU4rLAHDmOU7mkcbATQTcegWfkSTC0MCBhWfLy6fc5PwDHGI1xPBOj7RhTmtIdMMSUpwmhnOyCIUKYJSQTZAAOQlgihCSmZB8MKOGSUIaH4PbOvSrYt94s-lp11jVQNSVMP97eF6YxULWu7VxnNSysWyn_ZDxsVWNqaBuoXe280Z2qoVaNNv4Q7FWqDuZo-47A4-XsYXqd3NxfzacXN4mOH9OEcymFSqkoC1lypExZZBXOWEWpwoilqsKamUwWTNN4RcVFwWWpOErLshKMjsDZJrf17rk3octXNmhT13Ey14ecMMKyDGUpifT0D1263jdxuqgEYlkqBY3qfKO0dyF4U-Wtt3HddY5R_tVxHjvOvzuO9mSb2BcrU_7Kn1IjmGzAi63N-v-kfDadbyI_Afy0hVs</recordid><startdate>202101</startdate><enddate>202101</enddate><creator>Kosmidou, Vivian</creator><creator>Vlassi, Margarita</creator><creator>Anagiotos, Kyriakos</creator><creator>Raftopoulou, Sofia</creator><creator>Kalogerakou, Eirini</creator><creator>Skarmalioraki, Salomi</creator><creator>Aggeli, Chrysanthi</creator><creator>Choreftaki, Theodosia</creator><creator>Zografos, George</creator><creator>Pintzas, Alexander</creator><general>Blackwell Publishing Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6047-5361</orcidid></search><sort><creationdate>202101</creationdate><title>Noxa upregulation and 5‐gene apoptotic biomarker panel in colorectal cancer</title><author>Kosmidou, Vivian ; Vlassi, Margarita ; Anagiotos, Kyriakos ; Raftopoulou, Sofia ; Kalogerakou, Eirini ; Skarmalioraki, Salomi ; Aggeli, Chrysanthi ; Choreftaki, Theodosia ; Zografos, George ; Pintzas, Alexander</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2683-66887a537db8d60aedb9f194f33a1045af1c4e98b4c34c37f67b68da605ddf743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Apoptosis</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Colorectal carcinoma</topic><topic>Combinatorial analysis</topic><topic>CRC</topic><topic>Deregulation</topic><topic>Gene expression</topic><topic>Mcl-1 protein</topic><topic>Mutation</topic><topic>novel 5‐biomarker panel</topic><topic>Noxa early detection</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Surgery</topic><topic>Tissue analysis</topic><topic>Tissues</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kosmidou, Vivian</creatorcontrib><creatorcontrib>Vlassi, Margarita</creatorcontrib><creatorcontrib>Anagiotos, Kyriakos</creatorcontrib><creatorcontrib>Raftopoulou, Sofia</creatorcontrib><creatorcontrib>Kalogerakou, Eirini</creatorcontrib><creatorcontrib>Skarmalioraki, Salomi</creatorcontrib><creatorcontrib>Aggeli, Chrysanthi</creatorcontrib><creatorcontrib>Choreftaki, Theodosia</creatorcontrib><creatorcontrib>Zografos, George</creatorcontrib><creatorcontrib>Pintzas, Alexander</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kosmidou, Vivian</au><au>Vlassi, Margarita</au><au>Anagiotos, Kyriakos</au><au>Raftopoulou, Sofia</au><au>Kalogerakou, Eirini</au><au>Skarmalioraki, Salomi</au><au>Aggeli, Chrysanthi</au><au>Choreftaki, Theodosia</au><au>Zografos, George</au><au>Pintzas, Alexander</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Noxa upregulation and 5‐gene apoptotic biomarker panel in colorectal cancer</atitle><jtitle>European journal of clinical investigation</jtitle><addtitle>Eur J Clin Invest</addtitle><date>2021-01</date><risdate>2021</risdate><volume>51</volume><issue>1</issue><spage>e13353</spage><epage>n/a</epage><pages>e13353-n/a</pages><issn>0014-2972</issn><eissn>1365-2362</eissn><abstract>Background
NOXA and MCL1 are involved in the intrinsic pathway of apoptosis, where Noxa selectively binds to MCL1 and prevents it from inhibiting apoptosis. Both factors are considered as potential tumour biomarkers, while MCL1 has attracted interest as target in cancer. The purpose of this study was to investigate the expression of NOXA and MCL1 in 160 CRC tumour samples, to investigate their significance, also in combination with IAPs, DR5 expression and KRAS gene mutations in CRC.
Materials and methods
Fresh frozen colorectal tissue was obtained from patients undergoing surgery for CRC. Real‐time quantitative PCR was performed for the determination of mRNA expression levels. Protein expression was determined immunohistochemically. Differences in the mRNA expression profile were evaluated with the nonparametric Wilcoxon signed ranks test. Statistical analysis was performed with the use of Mann‐Whitney U test and receiver‐operating characteristic (ROC) curve.
Results
NOXA was found to be overexpressed in CRC tumours (P < .0001), even from early stage. Moreover, NOXA/MCL1 mRNA expression was significantly elevated in tumour samples compared to normal pairs (P < .0001). ROC curve analysis showed that both NOXA expression and its combination with Mcl1 expression have fair discriminatory value between CRC and normal colorectal tissue. Combinatorial ROC analysis revealed the most significant discriminatory value of NOXA, MCL1 with cIAP1 and cIAP2 (AUC = 0.834, P < .0001) as a 5‐gene panel of markers.
Conclusion
Noxa, Mcl1, DR5, cIAP1 and cIAP2 mRNA expressions are significantly deregulated in CRC and could provide a panel of markers with significant discriminatory value between CRC and normal colorectal tissue.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>32682341</pmid><doi>10.1111/eci.13353</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-6047-5361</orcidid></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Apoptosis Biomarkers Cancer Colorectal carcinoma Combinatorial analysis CRC Deregulation Gene expression Mcl-1 protein Mutation novel 5‐biomarker panel Noxa early detection Statistical analysis Statistical methods Surgery Tissue analysis Tissues Tumors |
| title | Noxa upregulation and 5‐gene apoptotic biomarker panel in colorectal cancer |
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