The utility of c‐Met as a diagnostic tissue biomarker in primary colorectal cancer
The transmembrane protein, c‐Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial. Tissue microarrays of matched normal...
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Veröffentlicht in: | International journal of experimental pathology 2021-06, Vol.102 (3), p.172-178 |
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creator | Armstrong, Gemma R. Khot, Mohammed Ibrahim Tiernan, Jim P. West, Nick P. Perry, Sarah L. Maisey, Tom I. Hughes, Thomas A. Jayne, David G. |
description | The transmembrane protein, c‐Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial.
Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c‐Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi‐quantifiable score, and differences in median scores analysed using the Wilcoxon signed‐rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c‐Met as a biomarker in CRC.
Epithelial cell membrane expression of c‐Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6‐15) versus median 6.00 (IQR 2.70‐12.00) respectively (P = |
doi_str_mv | 10.1111/iep.12395 |
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Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c‐Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi‐quantifiable score, and differences in median scores analysed using the Wilcoxon signed‐rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c‐Met as a biomarker in CRC.
Epithelial cell membrane expression of c‐Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6‐15) versus median 6.00 (IQR 2.70‐12.00) respectively (P = <.0001). ROC‐AUC analysis of c‐Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%‐89.45%) but sensitivity of only 30.92% (CI 25.37%‐36.90%).
Thus c‐Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c‐Met expression may have a role in diagnosis and prognostication if combined with other biomarkers.</description><identifier>ISSN: 0959-9673</identifier><identifier>EISSN: 1365-2613</identifier><identifier>DOI: 10.1111/iep.12395</identifier><identifier>PMID: 33951261</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>biomarker ; Biomarkers ; Cancer ; Cell membranes ; Colorectal cancer ; Colorectal carcinoma ; c‐Met ; Diagnostic systems ; Epithelial cells ; Epithelium ; Immunohistochemistry ; Rank tests ; Tissues</subject><ispartof>International journal of experimental pathology, 2021-06, Vol.102 (3), p.172-178</ispartof><rights>2021 The Authors. published by John Wiley & Sons Ltd on behalf of Company of the International Journal of Experimental Pathology (CIJEP).</rights><rights>2021 The Authors. International Journal of Experimental Pathology published by John Wiley & Sons Ltd on behalf of Company of the International Journal of Experimental Pathology (CIJEP).</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3885-30b2a10f74866d21bf215a26d369d60aa7752e8e2b261456b08cd429f21685653</citedby><cites>FETCH-LOGICAL-c3885-30b2a10f74866d21bf215a26d369d60aa7752e8e2b261456b08cd429f21685653</cites><orcidid>0000-0001-8179-8736</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%2Fiep.12395$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fiep.12395$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33951261$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Armstrong, Gemma R.</creatorcontrib><creatorcontrib>Khot, Mohammed Ibrahim</creatorcontrib><creatorcontrib>Tiernan, Jim P.</creatorcontrib><creatorcontrib>West, Nick P.</creatorcontrib><creatorcontrib>Perry, Sarah L.</creatorcontrib><creatorcontrib>Maisey, Tom I.</creatorcontrib><creatorcontrib>Hughes, Thomas A.</creatorcontrib><creatorcontrib>Jayne, David G.</creatorcontrib><title>The utility of c‐Met as a diagnostic tissue biomarker in primary colorectal cancer</title><title>International journal of experimental pathology</title><addtitle>Int J Exp Pathol</addtitle><description>The transmembrane protein, c‐Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial.
Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c‐Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi‐quantifiable score, and differences in median scores analysed using the Wilcoxon signed‐rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c‐Met as a biomarker in CRC.
Epithelial cell membrane expression of c‐Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6‐15) versus median 6.00 (IQR 2.70‐12.00) respectively (P = <.0001). ROC‐AUC analysis of c‐Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%‐89.45%) but sensitivity of only 30.92% (CI 25.37%‐36.90%).
Thus c‐Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c‐Met expression may have a role in diagnosis and prognostication if combined with other biomarkers.</description><subject>biomarker</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cell membranes</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>c‐Met</subject><subject>Diagnostic systems</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Immunohistochemistry</subject><subject>Rank tests</subject><subject>Tissues</subject><issn>0959-9673</issn><issn>1365-2613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp10L1OwzAUBWALgWgpDLwAssQCQ1r_1E4yoqpApSIYyhw5zg24pHGxE6FuPALPyJPgksKAhBfL0uejew9Cp5QMaTgjA-shZTwVe6hPuRQRk5Tvoz5JRRqlMuY9dOT9khDKGY0PUY8HSwPqo8XiGXDbmMo0G2xLrD_fP-6gwcpjhQujnmrrG6NxY7xvAefGrpR7AYdNjdfOhMcGa1tZB7pRFdaq1uCO0UGpKg8nu3uAHq-ni8ltNL-_mU2u5pHmSSIiTnKmKCnjcSJlwWheMioUkwWXaSGJUnEsGCTA8jDqWMicJLoYszQwmQgp-ABddLlrZ19b8E22Ml5DVakabOszJlj4KQkdB3r-hy5t6-ow3ValoaiYyqAuO6Wd9d5Bme12zCjJtlVnoersu-pgz3aJbb6C4lf-dBvAqANvpoLN_0nZbPrQRX4B6xCGnA</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Armstrong, Gemma R.</creator><creator>Khot, Mohammed Ibrahim</creator><creator>Tiernan, Jim P.</creator><creator>West, Nick P.</creator><creator>Perry, Sarah L.</creator><creator>Maisey, Tom I.</creator><creator>Hughes, Thomas A.</creator><creator>Jayne, David G.</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8179-8736</orcidid></search><sort><creationdate>202106</creationdate><title>The utility of c‐Met as a diagnostic tissue biomarker in primary colorectal cancer</title><author>Armstrong, Gemma R. ; Khot, Mohammed Ibrahim ; Tiernan, Jim P. ; West, Nick P. ; Perry, Sarah L. ; Maisey, Tom I. ; Hughes, Thomas A. ; Jayne, David G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3885-30b2a10f74866d21bf215a26d369d60aa7752e8e2b261456b08cd429f21685653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>biomarker</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Cell membranes</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>c‐Met</topic><topic>Diagnostic systems</topic><topic>Epithelial cells</topic><topic>Epithelium</topic><topic>Immunohistochemistry</topic><topic>Rank tests</topic><topic>Tissues</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Armstrong, Gemma R.</creatorcontrib><creatorcontrib>Khot, Mohammed Ibrahim</creatorcontrib><creatorcontrib>Tiernan, Jim P.</creatorcontrib><creatorcontrib>West, Nick P.</creatorcontrib><creatorcontrib>Perry, Sarah L.</creatorcontrib><creatorcontrib>Maisey, Tom I.</creatorcontrib><creatorcontrib>Hughes, Thomas A.</creatorcontrib><creatorcontrib>Jayne, David G.</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of experimental pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Armstrong, Gemma R.</au><au>Khot, Mohammed Ibrahim</au><au>Tiernan, Jim P.</au><au>West, Nick P.</au><au>Perry, Sarah L.</au><au>Maisey, Tom I.</au><au>Hughes, Thomas A.</au><au>Jayne, David G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The utility of c‐Met as a diagnostic tissue biomarker in primary colorectal cancer</atitle><jtitle>International journal of experimental pathology</jtitle><addtitle>Int J Exp Pathol</addtitle><date>2021-06</date><risdate>2021</risdate><volume>102</volume><issue>3</issue><spage>172</spage><epage>178</epage><pages>172-178</pages><issn>0959-9673</issn><eissn>1365-2613</eissn><abstract>The transmembrane protein, c‐Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial.
Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c‐Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi‐quantifiable score, and differences in median scores analysed using the Wilcoxon signed‐rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c‐Met as a biomarker in CRC.
Epithelial cell membrane expression of c‐Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6‐15) versus median 6.00 (IQR 2.70‐12.00) respectively (P = <.0001). ROC‐AUC analysis of c‐Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%‐89.45%) but sensitivity of only 30.92% (CI 25.37%‐36.90%).
Thus c‐Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c‐Met expression may have a role in diagnosis and prognostication if combined with other biomarkers.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33951261</pmid><doi>10.1111/iep.12395</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-8179-8736</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | biomarker Biomarkers Cancer Cell membranes Colorectal cancer Colorectal carcinoma c‐Met Diagnostic systems Epithelial cells Epithelium Immunohistochemistry Rank tests Tissues |
title | The utility of c‐Met as a diagnostic tissue biomarker in primary colorectal cancer |
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