Osteopontin Identified as Lead Marker of Colon Cancer Progression, Using Pooled Sample Expression Profiling
Background: New tumor markers and markers of tumor progression are needed for improved staging and for better assessment of treatment of many cancers. Gene expression profiling techniques offer the opportunity to discover such markers. We investigated the feasibility of sample pooling strategy in co...
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| Veröffentlicht in: | JNCI : Journal of the National Cancer Institute 2002-04, Vol.94 (7), p.513-521 |
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| creator | Agrawal, Deepak Chen, Tingan Irby, Rosalyn Quackenbush, John Chambers, Ann F. Szabo, Marianna Cantor, Alan Coppola, Domenico Yeatman, Timothy J. |
| description | Background: New tumor markers and markers of tumor progression are needed for improved staging and for better assessment of treatment of many cancers. Gene expression profiling techniques offer the opportunity to discover such markers. We investigated the feasibility of sample pooling strategy in combination with a novel analysis algorithm to identify markers. Methods: Total RNA from human colon tumors (n = 60) of multiple stages (adenomas; cancers with modified Astler Collier stages B, C, and D; and liver metastases) were pooled within stages and compared with pooled normal mucosal specimens (n = 10) by using oligonucleotide expression arrays. Genes that showed consistent increases or decreases in their expression through tumor progression were identified. Northern blot analysis was used to validate the findings. All statistical tests were two-sided. Results: More than 300 candidate tumor markers and more than 100 markers of tumor progression were identified. Northern analysis of 11 candidate tumor markers confirmed the gene expression changes. The gene for the secreted integrin-binding protein osteopontin was most consistently differentially expressed in conjunction with tumor progression. Its potential as a progression marker was validated (Spearman's ρ = 0.903; P |
| doi_str_mv | 10.1093/jnci/94.7.513 |
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| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71559189</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71559189</sourcerecordid><originalsourceid>FETCH-LOGICAL-c489t-fc5b260960c8486fca6e3afc76e3be9be10b79c4d4b47cacd9d2a3338799b5103</originalsourceid><addsrcrecordid>eNpdkc9rFDEUx4Modq0evUoQ9ORs83My7yhLtYWVVmqleAmZTFKynU3GZBfqf2-WDi6Yy5fwPnkvvA9CbylZUgL8bBNtOAOxVEtJ-TO0oKIlDaNEPkcLQphquk6JE_SqlA2pB5h4iU4oBQYg2QI9XJWdS1OKuxDx5eBq-uAGbApeOzPgbyY_uIyTx6s0pohXJtp6v87pPrtSQoqf8G0J8R5fpzTWhzdmO40Onz9Oc_3A-jBW5DV64c1Y3Js5T9Htl_Mfq4tmffX1cvV53VjRwa7xVvasJdAS24mu9da0jhtvVY3eQe8o6RVYMYheKGvsAAMznPNOAfSSEn6KPj71nXL6vXdlp7ehWDeOJrq0L1pRKYF2UMH3_4GbtM-x_k0zRkApRXiFmifI5lRKdl5POWxN_qMp0QcF-qBAg9BKVwWVfzc33fdbNxzpeecV-DADplgz-lxXGsqR44q2oqXHwaEqevxXr0J0q7iS-uLul775eQeSiu-a87-Cs57e</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>220977703</pqid></control><display><type>article</type><title>Osteopontin Identified as Lead Marker of Colon Cancer Progression, Using Pooled Sample Expression Profiling</title><source>MEDLINE</source><source>Oxford University Press Journals Current</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Agrawal, Deepak ; Chen, Tingan ; Irby, Rosalyn ; Quackenbush, John ; Chambers, Ann F. ; Szabo, Marianna ; Cantor, Alan ; Coppola, Domenico ; Yeatman, Timothy J.</creator><creatorcontrib>Agrawal, Deepak ; Chen, Tingan ; Irby, Rosalyn ; Quackenbush, John ; Chambers, Ann F. ; Szabo, Marianna ; Cantor, Alan ; Coppola, Domenico ; Yeatman, Timothy J.</creatorcontrib><description>Background: New tumor markers and markers of tumor progression are needed for improved staging and for better assessment of treatment of many cancers. Gene expression profiling techniques offer the opportunity to discover such markers. We investigated the feasibility of sample pooling strategy in combination with a novel analysis algorithm to identify markers. Methods: Total RNA from human colon tumors (n = 60) of multiple stages (adenomas; cancers with modified Astler Collier stages B, C, and D; and liver metastases) were pooled within stages and compared with pooled normal mucosal specimens (n = 10) by using oligonucleotide expression arrays. Genes that showed consistent increases or decreases in their expression through tumor progression were identified. Northern blot analysis was used to validate the findings. All statistical tests were two-sided. Results: More than 300 candidate tumor markers and more than 100 markers of tumor progression were identified. Northern analysis of 11 candidate tumor markers confirmed the gene expression changes. The gene for the secreted integrin-binding protein osteopontin was most consistently differentially expressed in conjunction with tumor progression. Its potential as a progression marker was validated (Spearman's ρ = 0.903; P<.001) with northern blot analysis using RNA from an independent set of 10 normal and 43 tumor samples representing all stages. Moreover, a statistically significant correlation between osteopontin protein expression and advancing tumor stage was identified with the use of 303 additional specimens (human cancer = 185, adenomas = 67, and normal mucosal specimens = 51) (Spearman's ρ = 0.667; P<.001). Conclusions: Sample pooling can be a powerful, cost-effective, and rapid means of identifying the most common changes in a gene expression profile. We identified osteopontin as a clinically useful marker of tumor progression by use of gene expression profiling on pooled samples.</description><identifier>ISSN: 0027-8874</identifier><identifier>ISSN: 1460-2105</identifier><identifier>EISSN: 1460-2105</identifier><identifier>DOI: 10.1093/jnci/94.7.513</identifier><identifier>PMID: 11929952</identifier><identifier>CODEN: JNCIEQ</identifier><language>eng</language><publisher>Cary, NC: Oxford University Press</publisher><subject>Adenoma - genetics ; Adenoma - metabolism ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Blotting, Northern ; Colonic Neoplasms - genetics ; Colonic Neoplasms - metabolism ; Disease Progression ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression ; Gene Expression Profiling ; Humans ; Immunoenzyme Techniques ; Medical sciences ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Osteopontin ; RNA, Messenger - metabolism ; Sialoglycoproteins - genetics ; Sialoglycoproteins - metabolism ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tumors</subject><ispartof>JNCI : Journal of the National Cancer Institute, 2002-04, Vol.94 (7), p.513-521</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Apr 3, 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-fc5b260960c8486fca6e3afc76e3be9be10b79c4d4b47cacd9d2a3338799b5103</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27906,27907</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13716461$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11929952$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Agrawal, Deepak</creatorcontrib><creatorcontrib>Chen, Tingan</creatorcontrib><creatorcontrib>Irby, Rosalyn</creatorcontrib><creatorcontrib>Quackenbush, John</creatorcontrib><creatorcontrib>Chambers, Ann F.</creatorcontrib><creatorcontrib>Szabo, Marianna</creatorcontrib><creatorcontrib>Cantor, Alan</creatorcontrib><creatorcontrib>Coppola, Domenico</creatorcontrib><creatorcontrib>Yeatman, Timothy J.</creatorcontrib><title>Osteopontin Identified as Lead Marker of Colon Cancer Progression, Using Pooled Sample Expression Profiling</title><title>JNCI : Journal of the National Cancer Institute</title><addtitle>JNCI J Natl Cancer Inst</addtitle><description>Background: New tumor markers and markers of tumor progression are needed for improved staging and for better assessment of treatment of many cancers. Gene expression profiling techniques offer the opportunity to discover such markers. We investigated the feasibility of sample pooling strategy in combination with a novel analysis algorithm to identify markers. Methods: Total RNA from human colon tumors (n = 60) of multiple stages (adenomas; cancers with modified Astler Collier stages B, C, and D; and liver metastases) were pooled within stages and compared with pooled normal mucosal specimens (n = 10) by using oligonucleotide expression arrays. Genes that showed consistent increases or decreases in their expression through tumor progression were identified. Northern blot analysis was used to validate the findings. All statistical tests were two-sided. Results: More than 300 candidate tumor markers and more than 100 markers of tumor progression were identified. Northern analysis of 11 candidate tumor markers confirmed the gene expression changes. The gene for the secreted integrin-binding protein osteopontin was most consistently differentially expressed in conjunction with tumor progression. Its potential as a progression marker was validated (Spearman's ρ = 0.903; P<.001) with northern blot analysis using RNA from an independent set of 10 normal and 43 tumor samples representing all stages. Moreover, a statistically significant correlation between osteopontin protein expression and advancing tumor stage was identified with the use of 303 additional specimens (human cancer = 185, adenomas = 67, and normal mucosal specimens = 51) (Spearman's ρ = 0.667; P<.001). Conclusions: Sample pooling can be a powerful, cost-effective, and rapid means of identifying the most common changes in a gene expression profile. We identified osteopontin as a clinically useful marker of tumor progression by use of gene expression profiling on pooled samples.</description><subject>Adenoma - genetics</subject><subject>Adenoma - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Blotting, Northern</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Disease Progression</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Medical sciences</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neoplasm Staging</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Osteopontin</subject><subject>RNA, Messenger - metabolism</subject><subject>Sialoglycoproteins - genetics</subject><subject>Sialoglycoproteins - metabolism</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Tumors</subject><issn>0027-8874</issn><issn>1460-2105</issn><issn>1460-2105</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc9rFDEUx4Modq0evUoQ9ORs83My7yhLtYWVVmqleAmZTFKynU3GZBfqf2-WDi6Yy5fwPnkvvA9CbylZUgL8bBNtOAOxVEtJ-TO0oKIlDaNEPkcLQphquk6JE_SqlA2pB5h4iU4oBQYg2QI9XJWdS1OKuxDx5eBq-uAGbApeOzPgbyY_uIyTx6s0pohXJtp6v87pPrtSQoqf8G0J8R5fpzTWhzdmO40Onz9Oc_3A-jBW5DV64c1Y3Js5T9Htl_Mfq4tmffX1cvV53VjRwa7xVvasJdAS24mu9da0jhtvVY3eQe8o6RVYMYheKGvsAAMznPNOAfSSEn6KPj71nXL6vXdlp7ehWDeOJrq0L1pRKYF2UMH3_4GbtM-x_k0zRkApRXiFmifI5lRKdl5POWxN_qMp0QcF-qBAg9BKVwWVfzc33fdbNxzpeecV-DADplgz-lxXGsqR44q2oqXHwaEqevxXr0J0q7iS-uLul775eQeSiu-a87-Cs57e</recordid><startdate>20020403</startdate><enddate>20020403</enddate><creator>Agrawal, Deepak</creator><creator>Chen, Tingan</creator><creator>Irby, Rosalyn</creator><creator>Quackenbush, John</creator><creator>Chambers, Ann F.</creator><creator>Szabo, Marianna</creator><creator>Cantor, Alan</creator><creator>Coppola, Domenico</creator><creator>Yeatman, Timothy J.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><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>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20020403</creationdate><title>Osteopontin Identified as Lead Marker of Colon Cancer Progression, Using Pooled Sample Expression Profiling</title><author>Agrawal, Deepak ; Chen, Tingan ; Irby, Rosalyn ; Quackenbush, John ; Chambers, Ann F. ; Szabo, Marianna ; Cantor, Alan ; Coppola, Domenico ; Yeatman, Timothy J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-fc5b260960c8486fca6e3afc76e3be9be10b79c4d4b47cacd9d2a3338799b5103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adenoma - genetics</topic><topic>Adenoma - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Blotting, Northern</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Disease Progression</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Medical sciences</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neoplasm Staging</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Osteopontin</topic><topic>RNA, Messenger - metabolism</topic><topic>Sialoglycoproteins - genetics</topic><topic>Sialoglycoproteins - metabolism</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Agrawal, Deepak</creatorcontrib><creatorcontrib>Chen, Tingan</creatorcontrib><creatorcontrib>Irby, Rosalyn</creatorcontrib><creatorcontrib>Quackenbush, John</creatorcontrib><creatorcontrib>Chambers, Ann F.</creatorcontrib><creatorcontrib>Szabo, Marianna</creatorcontrib><creatorcontrib>Cantor, Alan</creatorcontrib><creatorcontrib>Coppola, Domenico</creatorcontrib><creatorcontrib>Yeatman, Timothy J.</creatorcontrib><collection>Istex</collection><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>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>JNCI : Journal of the National Cancer Institute</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Agrawal, Deepak</au><au>Chen, Tingan</au><au>Irby, Rosalyn</au><au>Quackenbush, John</au><au>Chambers, Ann F.</au><au>Szabo, Marianna</au><au>Cantor, Alan</au><au>Coppola, Domenico</au><au>Yeatman, Timothy J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Osteopontin Identified as Lead Marker of Colon Cancer Progression, Using Pooled Sample Expression Profiling</atitle><jtitle>JNCI : Journal of the National Cancer Institute</jtitle><addtitle>JNCI J Natl Cancer Inst</addtitle><date>2002-04-03</date><risdate>2002</risdate><volume>94</volume><issue>7</issue><spage>513</spage><epage>521</epage><pages>513-521</pages><issn>0027-8874</issn><issn>1460-2105</issn><eissn>1460-2105</eissn><coden>JNCIEQ</coden><abstract>Background: New tumor markers and markers of tumor progression are needed for improved staging and for better assessment of treatment of many cancers. Gene expression profiling techniques offer the opportunity to discover such markers. We investigated the feasibility of sample pooling strategy in combination with a novel analysis algorithm to identify markers. Methods: Total RNA from human colon tumors (n = 60) of multiple stages (adenomas; cancers with modified Astler Collier stages B, C, and D; and liver metastases) were pooled within stages and compared with pooled normal mucosal specimens (n = 10) by using oligonucleotide expression arrays. Genes that showed consistent increases or decreases in their expression through tumor progression were identified. Northern blot analysis was used to validate the findings. All statistical tests were two-sided. Results: More than 300 candidate tumor markers and more than 100 markers of tumor progression were identified. Northern analysis of 11 candidate tumor markers confirmed the gene expression changes. The gene for the secreted integrin-binding protein osteopontin was most consistently differentially expressed in conjunction with tumor progression. Its potential as a progression marker was validated (Spearman's ρ = 0.903; P<.001) with northern blot analysis using RNA from an independent set of 10 normal and 43 tumor samples representing all stages. Moreover, a statistically significant correlation between osteopontin protein expression and advancing tumor stage was identified with the use of 303 additional specimens (human cancer = 185, adenomas = 67, and normal mucosal specimens = 51) (Spearman's ρ = 0.667; P<.001). Conclusions: Sample pooling can be a powerful, cost-effective, and rapid means of identifying the most common changes in a gene expression profile. We identified osteopontin as a clinically useful marker of tumor progression by use of gene expression profiling on pooled samples.</abstract><cop>Cary, NC</cop><pub>Oxford University Press</pub><pmid>11929952</pmid><doi>10.1093/jnci/94.7.513</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenoma - genetics Adenoma - metabolism Biological and medical sciences Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Blotting, Northern Colonic Neoplasms - genetics Colonic Neoplasms - metabolism Disease Progression Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Gene Expression Profiling Humans Immunoenzyme Techniques Medical sciences Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Neoplasm Staging Oligonucleotide Array Sequence Analysis Osteopontin RNA, Messenger - metabolism Sialoglycoproteins - genetics Sialoglycoproteins - metabolism Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors |
| title | Osteopontin Identified as Lead Marker of Colon Cancer Progression, Using Pooled Sample Expression Profiling |
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