Seromic profiling of colorectal cancer patients with novel glycopeptide microarray
Cancer‐associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post‐translational variants of proteins are likely to induce autoantibodies, and changes in O‐linked glycosylation represent one of the most important cancer‐associated post‐translational mo...
Gespeichert in:
| Veröffentlicht in: | International journal of cancer 2011-04, Vol.128 (8), p.1860-1871 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1871 |
|---|---|
| container_issue | 8 |
| container_start_page | 1860 |
| container_title | International journal of cancer |
| container_volume | 128 |
| creator | Pedersen, Johannes W. Blixt, Ola Bennett, Eric P. Tarp, Mads A. Dar, Imran Mandel, Ulla Poulsen, Steen S. Pedersen, Anders E. Rasmussen, Susanne Jess, Per Clausen, Henrik Wandall, Hans H. |
| description | Cancer‐associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post‐translational variants of proteins are likely to induce autoantibodies, and changes in O‐linked glycosylation represent one of the most important cancer‐associated post‐translational modifications (PTMs). Short aberrant O‐glycans on proteins may introduce novel glycopeptide epitopes that can elicit autoantibodies because of lack of tolerance. Technical barriers, however, have hampered detection of such glycopeptide‐specific autoantibodies. Here, we have constructed an expanded glycopeptide array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer‐associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer using novel monoclonal antibodies. Our study provides evidence for the value of glycopeptides and other PTM‐peptide arrays in diagnostic measures. |
| doi_str_mv | 10.1002/ijc.25778 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_853679494</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1399905917</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4228-ccd4c773bdab3b2d551d6e3bf9ff51289d2ba72e4ceb0b5a9e42ede66e5190803</originalsourceid><addsrcrecordid>eNp90MtOGzEUBmCromoCZdEXQN4g6GKIr-PxEkXQBkVC6mU98njOpI6c8WBPQHl7TBPKiq68OJ_-c_wj9IWSK0oIm7m1vWJSqeoDmlKiVUEYlUdommekUJSXE3Sc0poQSiURn9CEUS4EV2KKfvyEGDbO4iGGznnXr3DosA0-RLCj8dia3kLEgxkd9GPCT278g_vwCB6v_M6GAYbRtYBzRgwmRrP7jD52xic4Pbwn6Pftza_592J5_20xv14WVjBWFda2wirFm9Y0vGGtlLQtgTed7jpJWaVb1hjFQFhoSCONBsGghbIESTWpCD9BF_vcfPrDFtJYb1yy4L3pIWxTXUleKi20yPLyv5JyrTWRmqpMv-5p_k1KEbp6iG5j4q6mpH4pu85l13_LzvbsELttNtD-k6_tZnB-ACZZ47uYu3TpzXGtmJA0u9nePTkPu_c31ou7-X71M0rAluQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1399905917</pqid></control><display><type>article</type><title>Seromic profiling of colorectal cancer patients with novel glycopeptide microarray</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Pedersen, Johannes W. ; Blixt, Ola ; Bennett, Eric P. ; Tarp, Mads A. ; Dar, Imran ; Mandel, Ulla ; Poulsen, Steen S. ; Pedersen, Anders E. ; Rasmussen, Susanne ; Jess, Per ; Clausen, Henrik ; Wandall, Hans H.</creator><creatorcontrib>Pedersen, Johannes W. ; Blixt, Ola ; Bennett, Eric P. ; Tarp, Mads A. ; Dar, Imran ; Mandel, Ulla ; Poulsen, Steen S. ; Pedersen, Anders E. ; Rasmussen, Susanne ; Jess, Per ; Clausen, Henrik ; Wandall, Hans H.</creatorcontrib><description>Cancer‐associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post‐translational variants of proteins are likely to induce autoantibodies, and changes in O‐linked glycosylation represent one of the most important cancer‐associated post‐translational modifications (PTMs). Short aberrant O‐glycans on proteins may introduce novel glycopeptide epitopes that can elicit autoantibodies because of lack of tolerance. Technical barriers, however, have hampered detection of such glycopeptide‐specific autoantibodies. Here, we have constructed an expanded glycopeptide array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer‐associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer using novel monoclonal antibodies. Our study provides evidence for the value of glycopeptides and other PTM‐peptide arrays in diagnostic measures.</description><identifier>ISSN: 0020-7136</identifier><identifier>ISSN: 1097-0215</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.25778</identifier><identifier>PMID: 21344374</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Antibodies, Monoclonal - immunology ; autoantibodies ; Autoantibodies - immunology ; Biological and medical sciences ; biomarkers ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - immunology ; cancer ; Case-Control Studies ; colon ; Colorectal Neoplasms - blood ; Colorectal Neoplasms - diagnosis ; Colorectal Neoplasms - immunology ; Enzyme-Linked Immunosorbent Assay ; Epitopes - analysis ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; glycopeptide ; Glycopeptides - blood ; Glycopeptides - immunology ; Glycosylation ; Humans ; Immunoenzyme Techniques ; Male ; Medical sciences ; microarray ; Middle Aged ; Mucins - blood ; Mucins - immunology ; Prognosis ; Protein Array Analysis ; Protein Processing, Post-Translational ; Recombinant Proteins - immunology ; Recombinant Proteins - metabolism ; rectum ; seromic profiling ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tumors</subject><ispartof>International journal of cancer, 2011-04, Vol.128 (8), p.1860-1871</ispartof><rights>Copyright © 2011 UICC</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 UICC.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4228-ccd4c773bdab3b2d551d6e3bf9ff51289d2ba72e4ceb0b5a9e42ede66e5190803</citedby><cites>FETCH-LOGICAL-c4228-ccd4c773bdab3b2d551d6e3bf9ff51289d2ba72e4ceb0b5a9e42ede66e5190803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.25778$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.25778$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23972451$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21344374$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pedersen, Johannes W.</creatorcontrib><creatorcontrib>Blixt, Ola</creatorcontrib><creatorcontrib>Bennett, Eric P.</creatorcontrib><creatorcontrib>Tarp, Mads A.</creatorcontrib><creatorcontrib>Dar, Imran</creatorcontrib><creatorcontrib>Mandel, Ulla</creatorcontrib><creatorcontrib>Poulsen, Steen S.</creatorcontrib><creatorcontrib>Pedersen, Anders E.</creatorcontrib><creatorcontrib>Rasmussen, Susanne</creatorcontrib><creatorcontrib>Jess, Per</creatorcontrib><creatorcontrib>Clausen, Henrik</creatorcontrib><creatorcontrib>Wandall, Hans H.</creatorcontrib><title>Seromic profiling of colorectal cancer patients with novel glycopeptide microarray</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>Cancer‐associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post‐translational variants of proteins are likely to induce autoantibodies, and changes in O‐linked glycosylation represent one of the most important cancer‐associated post‐translational modifications (PTMs). Short aberrant O‐glycans on proteins may introduce novel glycopeptide epitopes that can elicit autoantibodies because of lack of tolerance. Technical barriers, however, have hampered detection of such glycopeptide‐specific autoantibodies. Here, we have constructed an expanded glycopeptide array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer‐associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer using novel monoclonal antibodies. Our study provides evidence for the value of glycopeptides and other PTM‐peptide arrays in diagnostic measures.</description><subject>Antibodies, Monoclonal - immunology</subject><subject>autoantibodies</subject><subject>Autoantibodies - immunology</subject><subject>Biological and medical sciences</subject><subject>biomarkers</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biomarkers, Tumor - immunology</subject><subject>cancer</subject><subject>Case-Control Studies</subject><subject>colon</subject><subject>Colorectal Neoplasms - blood</subject><subject>Colorectal Neoplasms - diagnosis</subject><subject>Colorectal Neoplasms - immunology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epitopes - analysis</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>glycopeptide</subject><subject>Glycopeptides - blood</subject><subject>Glycopeptides - immunology</subject><subject>Glycosylation</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>microarray</subject><subject>Middle Aged</subject><subject>Mucins - blood</subject><subject>Mucins - immunology</subject><subject>Prognosis</subject><subject>Protein Array Analysis</subject><subject>Protein Processing, Post-Translational</subject><subject>Recombinant Proteins - immunology</subject><subject>Recombinant Proteins - metabolism</subject><subject>rectum</subject><subject>seromic profiling</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Tumors</subject><issn>0020-7136</issn><issn>1097-0215</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90MtOGzEUBmCromoCZdEXQN4g6GKIr-PxEkXQBkVC6mU98njOpI6c8WBPQHl7TBPKiq68OJ_-c_wj9IWSK0oIm7m1vWJSqeoDmlKiVUEYlUdommekUJSXE3Sc0poQSiURn9CEUS4EV2KKfvyEGDbO4iGGznnXr3DosA0-RLCj8dia3kLEgxkd9GPCT278g_vwCB6v_M6GAYbRtYBzRgwmRrP7jD52xic4Pbwn6Pftza_592J5_20xv14WVjBWFda2wirFm9Y0vGGtlLQtgTed7jpJWaVb1hjFQFhoSCONBsGghbIESTWpCD9BF_vcfPrDFtJYb1yy4L3pIWxTXUleKi20yPLyv5JyrTWRmqpMv-5p_k1KEbp6iG5j4q6mpH4pu85l13_LzvbsELttNtD-k6_tZnB-ACZZ47uYu3TpzXGtmJA0u9nePTkPu_c31ou7-X71M0rAluQ</recordid><startdate>20110415</startdate><enddate>20110415</enddate><creator>Pedersen, Johannes W.</creator><creator>Blixt, Ola</creator><creator>Bennett, Eric P.</creator><creator>Tarp, Mads A.</creator><creator>Dar, Imran</creator><creator>Mandel, Ulla</creator><creator>Poulsen, Steen S.</creator><creator>Pedersen, Anders E.</creator><creator>Rasmussen, Susanne</creator><creator>Jess, Per</creator><creator>Clausen, Henrik</creator><creator>Wandall, Hans H.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Blackwell</general><scope>IQODW</scope><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20110415</creationdate><title>Seromic profiling of colorectal cancer patients with novel glycopeptide microarray</title><author>Pedersen, Johannes W. ; Blixt, Ola ; Bennett, Eric P. ; Tarp, Mads A. ; Dar, Imran ; Mandel, Ulla ; Poulsen, Steen S. ; Pedersen, Anders E. ; Rasmussen, Susanne ; Jess, Per ; Clausen, Henrik ; Wandall, Hans H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4228-ccd4c773bdab3b2d551d6e3bf9ff51289d2ba72e4ceb0b5a9e42ede66e5190803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Antibodies, Monoclonal - immunology</topic><topic>autoantibodies</topic><topic>Autoantibodies - immunology</topic><topic>Biological and medical sciences</topic><topic>biomarkers</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biomarkers, Tumor - immunology</topic><topic>cancer</topic><topic>Case-Control Studies</topic><topic>colon</topic><topic>Colorectal Neoplasms - blood</topic><topic>Colorectal Neoplasms - diagnosis</topic><topic>Colorectal Neoplasms - immunology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epitopes - analysis</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>glycopeptide</topic><topic>Glycopeptides - blood</topic><topic>Glycopeptides - immunology</topic><topic>Glycosylation</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>microarray</topic><topic>Middle Aged</topic><topic>Mucins - blood</topic><topic>Mucins - immunology</topic><topic>Prognosis</topic><topic>Protein Array Analysis</topic><topic>Protein Processing, Post-Translational</topic><topic>Recombinant Proteins - immunology</topic><topic>Recombinant Proteins - metabolism</topic><topic>rectum</topic><topic>seromic profiling</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pedersen, Johannes W.</creatorcontrib><creatorcontrib>Blixt, Ola</creatorcontrib><creatorcontrib>Bennett, Eric P.</creatorcontrib><creatorcontrib>Tarp, Mads A.</creatorcontrib><creatorcontrib>Dar, Imran</creatorcontrib><creatorcontrib>Mandel, Ulla</creatorcontrib><creatorcontrib>Poulsen, Steen S.</creatorcontrib><creatorcontrib>Pedersen, Anders E.</creatorcontrib><creatorcontrib>Rasmussen, Susanne</creatorcontrib><creatorcontrib>Jess, Per</creatorcontrib><creatorcontrib>Clausen, Henrik</creatorcontrib><creatorcontrib>Wandall, Hans H.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pedersen, Johannes W.</au><au>Blixt, Ola</au><au>Bennett, Eric P.</au><au>Tarp, Mads A.</au><au>Dar, Imran</au><au>Mandel, Ulla</au><au>Poulsen, Steen S.</au><au>Pedersen, Anders E.</au><au>Rasmussen, Susanne</au><au>Jess, Per</au><au>Clausen, Henrik</au><au>Wandall, Hans H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Seromic profiling of colorectal cancer patients with novel glycopeptide microarray</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2011-04-15</date><risdate>2011</risdate><volume>128</volume><issue>8</issue><spage>1860</spage><epage>1871</epage><pages>1860-1871</pages><issn>0020-7136</issn><issn>1097-0215</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>Cancer‐associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post‐translational variants of proteins are likely to induce autoantibodies, and changes in O‐linked glycosylation represent one of the most important cancer‐associated post‐translational modifications (PTMs). Short aberrant O‐glycans on proteins may introduce novel glycopeptide epitopes that can elicit autoantibodies because of lack of tolerance. Technical barriers, however, have hampered detection of such glycopeptide‐specific autoantibodies. Here, we have constructed an expanded glycopeptide array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer‐associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer using novel monoclonal antibodies. Our study provides evidence for the value of glycopeptides and other PTM‐peptide arrays in diagnostic measures.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21344374</pmid><doi>10.1002/ijc.25778</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0020-7136 |
| ispartof | International journal of cancer, 2011-04, Vol.128 (8), p.1860-1871 |
| issn | 0020-7136 1097-0215 1097-0215 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_853679494 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Antibodies, Monoclonal - immunology autoantibodies Autoantibodies - immunology Biological and medical sciences biomarkers Biomarkers, Tumor - analysis Biomarkers, Tumor - immunology cancer Case-Control Studies colon Colorectal Neoplasms - blood Colorectal Neoplasms - diagnosis Colorectal Neoplasms - immunology Enzyme-Linked Immunosorbent Assay Epitopes - analysis Female Gastroenterology. Liver. Pancreas. Abdomen glycopeptide Glycopeptides - blood Glycopeptides - immunology Glycosylation Humans Immunoenzyme Techniques Male Medical sciences microarray Middle Aged Mucins - blood Mucins - immunology Prognosis Protein Array Analysis Protein Processing, Post-Translational Recombinant Proteins - immunology Recombinant Proteins - metabolism rectum seromic profiling Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors |
| title | Seromic profiling of colorectal cancer patients with novel glycopeptide microarray |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T08%3A06%3A08IST&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=Seromic%20profiling%20of%20colorectal%20cancer%20patients%20with%20novel%20glycopeptide%20microarray&rft.jtitle=International%20journal%20of%20cancer&rft.au=Pedersen,%20Johannes%20W.&rft.date=2011-04-15&rft.volume=128&rft.issue=8&rft.spage=1860&rft.epage=1871&rft.pages=1860-1871&rft.issn=0020-7136&rft.eissn=1097-0215&rft.coden=IJCNAW&rft_id=info:doi/10.1002/ijc.25778&rft_dat=%3Cproquest_cross%3E1399905917%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=1399905917&rft_id=info:pmid/21344374&rfr_iscdi=true |