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High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients

BACKGROUND: The metastasis-associated in colon cancer 1 (MACC1) gene has been identified as prognostic biomarker for colorectal cancer (CRC). Here, we aimed at the refinement of risk assessment by separate and combined survival analyses of MACC1 expression with any of the markers KRAS mutated in cod...

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Autores principales: Ilm, Katharina, Kemmner, Wolfgang, Osterland, Marc, Burock, Susen, Koch, Gudrun, Herrmann, Pia, Schlag, Peter M, Stein, Ulrike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335361/
https://www.ncbi.nlm.nih.gov/pubmed/25742883
http://dx.doi.org/10.1186/s12943-015-0316-2
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author Ilm, Katharina
Kemmner, Wolfgang
Osterland, Marc
Burock, Susen
Koch, Gudrun
Herrmann, Pia
Schlag, Peter M
Stein, Ulrike
author_facet Ilm, Katharina
Kemmner, Wolfgang
Osterland, Marc
Burock, Susen
Koch, Gudrun
Herrmann, Pia
Schlag, Peter M
Stein, Ulrike
author_sort Ilm, Katharina
collection PubMed
description BACKGROUND: The metastasis-associated in colon cancer 1 (MACC1) gene has been identified as prognostic biomarker for colorectal cancer (CRC). Here, we aimed at the refinement of risk assessment by separate and combined survival analyses of MACC1 expression with any of the markers KRAS mutated in codon 12 (KRAS G12) or codon 13 (KRAS G13), BRAF V600 mutation and MSI status in a retrospective study of 99 CRC patients with tumors UICC staged I, II and III. FINDINGS: We showed that only high MACC1 expression (HR: 6.09, 95% CI: 2.50-14.85, P < 0.001) and KRAS G13 mutation (HR: 5.19, 95% CI: 1.06-25.45, P = 0.042) were independent prognostic markers for shorter metastasis-free survival (MFS). Accordingly, Cox regression analysis revealed that patients with high MACC1 expression and KRAS G13 mutation exhibited the worst prognosis (HR: 14.48, 95% CI: 3.37-62.18, P < 0.001). Patients were classified based on their molecular characteristics into four clusters with significant differences in MFS (P = 0.003) by using the SPSS 2-step cluster function and Kaplan-Meier survival analysis. CONCLUSION: According to our results, patients with high MACC1 expression and mutated KRAS G13 exhibited the highest risk for metachronous metastases formation. Moreover, we demonstrated that the “Traditional pathway” with an intermediate risk for metastasis formation can be further subdivided by assessing MACC1 expression into a low and high risk group with regard to MFS prognosis. This is the first report showing that identification of CRC patients at high risk for metastasis is possible by assessing MACC1 expression in combination with KRAS G13 mutation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0316-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-43353612015-02-21 High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients Ilm, Katharina Kemmner, Wolfgang Osterland, Marc Burock, Susen Koch, Gudrun Herrmann, Pia Schlag, Peter M Stein, Ulrike Mol Cancer Short Communication BACKGROUND: The metastasis-associated in colon cancer 1 (MACC1) gene has been identified as prognostic biomarker for colorectal cancer (CRC). Here, we aimed at the refinement of risk assessment by separate and combined survival analyses of MACC1 expression with any of the markers KRAS mutated in codon 12 (KRAS G12) or codon 13 (KRAS G13), BRAF V600 mutation and MSI status in a retrospective study of 99 CRC patients with tumors UICC staged I, II and III. FINDINGS: We showed that only high MACC1 expression (HR: 6.09, 95% CI: 2.50-14.85, P < 0.001) and KRAS G13 mutation (HR: 5.19, 95% CI: 1.06-25.45, P = 0.042) were independent prognostic markers for shorter metastasis-free survival (MFS). Accordingly, Cox regression analysis revealed that patients with high MACC1 expression and KRAS G13 mutation exhibited the worst prognosis (HR: 14.48, 95% CI: 3.37-62.18, P < 0.001). Patients were classified based on their molecular characteristics into four clusters with significant differences in MFS (P = 0.003) by using the SPSS 2-step cluster function and Kaplan-Meier survival analysis. CONCLUSION: According to our results, patients with high MACC1 expression and mutated KRAS G13 exhibited the highest risk for metachronous metastases formation. Moreover, we demonstrated that the “Traditional pathway” with an intermediate risk for metastasis formation can be further subdivided by assessing MACC1 expression into a low and high risk group with regard to MFS prognosis. This is the first report showing that identification of CRC patients at high risk for metastasis is possible by assessing MACC1 expression in combination with KRAS G13 mutation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0316-2) contains supplementary material, which is available to authorized users. BioMed Central 2015-02-14 /pmc/articles/PMC4335361/ /pubmed/25742883 http://dx.doi.org/10.1186/s12943-015-0316-2 Text en © Ilm et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Communication
Ilm, Katharina
Kemmner, Wolfgang
Osterland, Marc
Burock, Susen
Koch, Gudrun
Herrmann, Pia
Schlag, Peter M
Stein, Ulrike
High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients
title High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients
title_full High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients
title_fullStr High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients
title_full_unstemmed High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients
title_short High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients
title_sort high macc1 expression in combination with mutated kras g13 indicates poor survival of colorectal cancer patients
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335361/
https://www.ncbi.nlm.nih.gov/pubmed/25742883
http://dx.doi.org/10.1186/s12943-015-0316-2
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