Immunoprofiles of 11 Biomarkers Using Tissue Microarrays Identify Prognostic Subgroups in Colorectal Cancer
BACKGROUND, AIMS: Genomewide expression profiling has identified a number of genes expressed at higher levels in colorectal cancer (CRC) than in normal tissues. Our objectives in this study were: 1) to test whether genes were also distinct on the protein level; 2) to evaluate these biomarkers in a s...
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Elsevier
2005-08-01
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Series: | Neoplasia: An International Journal for Oncology Research |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S147655860580106X |
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author | Thomas Knösel Anna Emde Karsten Schlüns Yuan Chen Karsten Jürchott Matthias Krause Manfred Dietel Iver Petersen |
author_facet | Thomas Knösel Anna Emde Karsten Schlüns Yuan Chen Karsten Jürchott Matthias Krause Manfred Dietel Iver Petersen |
author_sort | Thomas Knösel |
collection | DOAJ |
description | BACKGROUND, AIMS: Genomewide expression profiling has identified a number of genes expressed at higher levels in colorectal cancer (CRC) than in normal tissues. Our objectives in this study were: 1) to test whether genes were also distinct on the protein level; 2) to evaluate these biomarkers in a series of well-characterized CRCs;, 3) to apply hierarchical cluster analysis to the immunohistochemical data. METHODS: Tissue microarrays (TMAs) comprising 351 CRC specimens from 270 patients were constructed to evaluate the genes Adam10, CyclinD1, Annexinll, NFKB, Casein-kinase-2-beta (CK2B), YB-1, P32, Rad51, c-fos, IGFBP4, Connexin26 (Cx26). In total, 3,797 samples were analyzed. RESULTS: Unsupervised hierarchical clustering discovered subgroups of CRC that differed by tumor stage, survival. KaplanMeier analysis showed that reduced Cx26 expression was significantly associated with shorter patient survival, higher tumor grade (G1/G2vs G3, P = .02), Adam10 expression with a higher tumor stage (pT1/2vs pT3/4, P = .04). CONCLUSIONS: Our study highlights the potential of TMAs for a higher-dimensional analysis by evaluating serial sections of the same tissue core (three-dimensional TMA analysis). In addition, it endorses the use of immunohistochemistry supplemented by hierarchical clustering for the identification of tumor subgroups with diagnostic, prognostic signatures. |
first_indexed | 2024-04-12T14:22:05Z |
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institution | Directory Open Access Journal |
issn | 1476-5586 1522-8002 |
language | English |
last_indexed | 2024-04-12T14:22:05Z |
publishDate | 2005-08-01 |
publisher | Elsevier |
record_format | Article |
series | Neoplasia: An International Journal for Oncology Research |
spelling | doaj.art-99f54b8c71ee4491855c0066c0a501d72022-12-22T03:29:32ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022005-08-017874174710.1593/neo.05178Immunoprofiles of 11 Biomarkers Using Tissue Microarrays Identify Prognostic Subgroups in Colorectal CancerThomas Knösel0Anna Emde1Karsten Schlüns2Yuan Chen3Karsten Jürchott4Matthias Krause5Manfred Dietel6Iver Petersen7Institute of Pathology, Charite-Campus Mitte, Berlin, GermanyInstitute of Pathology, Charite-Campus Mitte, Berlin, GermanyInstitute of Pathology, Charite-Campus Mitte, Berlin, GermanyInstitute of Pathology, Charite-Campus Mitte, Berlin, GermanyInstitute of Pathology, Charite-Campus Mitte, Berlin, GermanyDepartment of Surgery, Oncology, RRC, Charite Campus Buch, Berlin, GermanyInstitute of Pathology, Charite-Campus Mitte, Berlin, GermanyInstitute of Pathology, Charite-Campus Mitte, Berlin, GermanyBACKGROUND, AIMS: Genomewide expression profiling has identified a number of genes expressed at higher levels in colorectal cancer (CRC) than in normal tissues. Our objectives in this study were: 1) to test whether genes were also distinct on the protein level; 2) to evaluate these biomarkers in a series of well-characterized CRCs;, 3) to apply hierarchical cluster analysis to the immunohistochemical data. METHODS: Tissue microarrays (TMAs) comprising 351 CRC specimens from 270 patients were constructed to evaluate the genes Adam10, CyclinD1, Annexinll, NFKB, Casein-kinase-2-beta (CK2B), YB-1, P32, Rad51, c-fos, IGFBP4, Connexin26 (Cx26). In total, 3,797 samples were analyzed. RESULTS: Unsupervised hierarchical clustering discovered subgroups of CRC that differed by tumor stage, survival. KaplanMeier analysis showed that reduced Cx26 expression was significantly associated with shorter patient survival, higher tumor grade (G1/G2vs G3, P = .02), Adam10 expression with a higher tumor stage (pT1/2vs pT3/4, P = .04). CONCLUSIONS: Our study highlights the potential of TMAs for a higher-dimensional analysis by evaluating serial sections of the same tissue core (three-dimensional TMA analysis). In addition, it endorses the use of immunohistochemistry supplemented by hierarchical clustering for the identification of tumor subgroups with diagnostic, prognostic signatures.http://www.sciencedirect.com/science/article/pii/S147655860580106XConnexin26 (Cx26)Adam10colorectal cancer (CRC)hierarchical clusteringtissue microarray (TMA) |
spellingShingle | Thomas Knösel Anna Emde Karsten Schlüns Yuan Chen Karsten Jürchott Matthias Krause Manfred Dietel Iver Petersen Immunoprofiles of 11 Biomarkers Using Tissue Microarrays Identify Prognostic Subgroups in Colorectal Cancer Neoplasia: An International Journal for Oncology Research Connexin26 (Cx26) Adam10 colorectal cancer (CRC) hierarchical clustering tissue microarray (TMA) |
title | Immunoprofiles of 11 Biomarkers Using Tissue Microarrays Identify Prognostic Subgroups in Colorectal Cancer |
title_full | Immunoprofiles of 11 Biomarkers Using Tissue Microarrays Identify Prognostic Subgroups in Colorectal Cancer |
title_fullStr | Immunoprofiles of 11 Biomarkers Using Tissue Microarrays Identify Prognostic Subgroups in Colorectal Cancer |
title_full_unstemmed | Immunoprofiles of 11 Biomarkers Using Tissue Microarrays Identify Prognostic Subgroups in Colorectal Cancer |
title_short | Immunoprofiles of 11 Biomarkers Using Tissue Microarrays Identify Prognostic Subgroups in Colorectal Cancer |
title_sort | immunoprofiles of 11 biomarkers using tissue microarrays identify prognostic subgroups in colorectal cancer |
topic | Connexin26 (Cx26) Adam10 colorectal cancer (CRC) hierarchical clustering tissue microarray (TMA) |
url | http://www.sciencedirect.com/science/article/pii/S147655860580106X |
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