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Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy
Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis‐promoting protein S100A4 predicts poor outcome in colorectal cancer, bu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971912/ https://www.ncbi.nlm.nih.gov/pubmed/27273130 http://dx.doi.org/10.1002/cam4.766 |
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author | Boye, Kjetil Jacob, Havjin Frikstad, Kari‐Anne M. Nesland, Jahn M. Mælandsmo, Gunhild M. Dahl, Olav Nesbakken, Arild Flatmark, Kjersti |
author_facet | Boye, Kjetil Jacob, Havjin Frikstad, Kari‐Anne M. Nesland, Jahn M. Mælandsmo, Gunhild M. Dahl, Olav Nesbakken, Arild Flatmark, Kjersti |
author_sort | Boye, Kjetil |
collection | PubMed |
description | Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis‐promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population‐representative cohort and a randomized phase III study on adjuvant 5‐fluorouracil/levamisole. Sensitivity to treatment with 5‐fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse‐free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse‐free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5‐fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5‐fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine‐based chemotherapy is limited. |
format | Online Article Text |
id | pubmed-4971912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-49719122016-08-11 Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy Boye, Kjetil Jacob, Havjin Frikstad, Kari‐Anne M. Nesland, Jahn M. Mælandsmo, Gunhild M. Dahl, Olav Nesbakken, Arild Flatmark, Kjersti Cancer Med Clinical Cancer Research Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis‐promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population‐representative cohort and a randomized phase III study on adjuvant 5‐fluorouracil/levamisole. Sensitivity to treatment with 5‐fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse‐free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse‐free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5‐fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5‐fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine‐based chemotherapy is limited. John Wiley and Sons Inc. 2016-06-08 /pmc/articles/PMC4971912/ /pubmed/27273130 http://dx.doi.org/10.1002/cam4.766 Text en © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Cancer Research Boye, Kjetil Jacob, Havjin Frikstad, Kari‐Anne M. Nesland, Jahn M. Mælandsmo, Gunhild M. Dahl, Olav Nesbakken, Arild Flatmark, Kjersti Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy |
title | Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy |
title_full | Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy |
title_fullStr | Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy |
title_full_unstemmed | Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy |
title_short | Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy |
title_sort | prognostic significance of s100a4 expression in stage ii and iii colorectal cancer: results from a population‐based series and a randomized phase iii study on adjuvant chemotherapy |
topic | Clinical Cancer Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971912/ https://www.ncbi.nlm.nih.gov/pubmed/27273130 http://dx.doi.org/10.1002/cam4.766 |
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