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Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis

BACKGROUND: Molecular differences in colorectal cancer (CRC) are associated with the metastatic route. Patient survival is mainly driven by metastatic spread thus it is imperative to understand its key drivers to develop biomarkers for risk stratification, follow-up protocols and personalized therap...

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Autores principales: Jacob, Sven, Bösch, Florian, Schoenberg, Markus B., Pretzsch, Elise, Lampert, Christopher, Haoyu, Ren, Renz, Bernhard W., Michl, Marlies, Kumbrink, Jörg, Kirchner, Thomas, Werner, Jens, Angele, Martin K., Neumann, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8603526/
https://www.ncbi.nlm.nih.gov/pubmed/34794407
http://dx.doi.org/10.1186/s12885-021-08927-w
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author Jacob, Sven
Bösch, Florian
Schoenberg, Markus B.
Pretzsch, Elise
Lampert, Christopher
Haoyu, Ren
Renz, Bernhard W.
Michl, Marlies
Kumbrink, Jörg
Kirchner, Thomas
Werner, Jens
Angele, Martin K.
Neumann, Jens
author_facet Jacob, Sven
Bösch, Florian
Schoenberg, Markus B.
Pretzsch, Elise
Lampert, Christopher
Haoyu, Ren
Renz, Bernhard W.
Michl, Marlies
Kumbrink, Jörg
Kirchner, Thomas
Werner, Jens
Angele, Martin K.
Neumann, Jens
author_sort Jacob, Sven
collection PubMed
description BACKGROUND: Molecular differences in colorectal cancer (CRC) are associated with the metastatic route. Patient survival is mainly driven by metastatic spread thus it is imperative to understand its key drivers to develop biomarkers for risk stratification, follow-up protocols and personalized therapy. Thus, this study aimed to identify genes associated with the metastatic route in CRC. MATERIAL AND METHODS: CRC patients resected at our clinic from 2005 to 2014 and with a minimum 5-year follow-up were included in this analysis and grouped into CRC with hepatic (HEP), peritoneal (PER) or without distant metastases (M0), and HEP/PER. Firstly, tumor RNA of 6 patients each was isolated by microdissection from formalin-fixed paraffin-embedded specimens and analyzed by a NanoString analysis. Subsequently, these results were validated with immunohistochemistry and correlated to clinicopathological parameters in a larger collective of CRC patients (HEP n = 51, PER n = 44, M0 n = 47, HEP/PER n = 28). RESULTS: Compared to M0, HEP tumors showed 20 differentially expressed genes associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Compared to M0, PER tumors had 18 differentially expressed genes. The finding of different gene signatures was supported by the multidimensional principal component clustering analysis. Tumor perforation did not influence the metastatic route. CIB1 was homogenously and significantly overexpressed in HEP compared to M0 (p < 0.001), but not in PER. Furthermore, immunohistochemical validation demonstrated that the mean CIB1 expression in HEP was 80% higher than in M0 (p < 0.001). CONCLUSION: Gene expression analysis revealed that CIB1 is significantly overexpressed in CRC leading to liver metastases compared to M0 and PER. Thus, the present results suggest that CIB1 may play a crucial role for hematogenous spread to the liver but not for peritoneal carcinomatosis. Consequently, CIB1 seems to be a promising prognostic marker and a potential tool for future targeted therapies as well as early diagnostics and follow-up.
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spelling pubmed-86035262021-11-19 Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis Jacob, Sven Bösch, Florian Schoenberg, Markus B. Pretzsch, Elise Lampert, Christopher Haoyu, Ren Renz, Bernhard W. Michl, Marlies Kumbrink, Jörg Kirchner, Thomas Werner, Jens Angele, Martin K. Neumann, Jens BMC Cancer Research BACKGROUND: Molecular differences in colorectal cancer (CRC) are associated with the metastatic route. Patient survival is mainly driven by metastatic spread thus it is imperative to understand its key drivers to develop biomarkers for risk stratification, follow-up protocols and personalized therapy. Thus, this study aimed to identify genes associated with the metastatic route in CRC. MATERIAL AND METHODS: CRC patients resected at our clinic from 2005 to 2014 and with a minimum 5-year follow-up were included in this analysis and grouped into CRC with hepatic (HEP), peritoneal (PER) or without distant metastases (M0), and HEP/PER. Firstly, tumor RNA of 6 patients each was isolated by microdissection from formalin-fixed paraffin-embedded specimens and analyzed by a NanoString analysis. Subsequently, these results were validated with immunohistochemistry and correlated to clinicopathological parameters in a larger collective of CRC patients (HEP n = 51, PER n = 44, M0 n = 47, HEP/PER n = 28). RESULTS: Compared to M0, HEP tumors showed 20 differentially expressed genes associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Compared to M0, PER tumors had 18 differentially expressed genes. The finding of different gene signatures was supported by the multidimensional principal component clustering analysis. Tumor perforation did not influence the metastatic route. CIB1 was homogenously and significantly overexpressed in HEP compared to M0 (p < 0.001), but not in PER. Furthermore, immunohistochemical validation demonstrated that the mean CIB1 expression in HEP was 80% higher than in M0 (p < 0.001). CONCLUSION: Gene expression analysis revealed that CIB1 is significantly overexpressed in CRC leading to liver metastases compared to M0 and PER. Thus, the present results suggest that CIB1 may play a crucial role for hematogenous spread to the liver but not for peritoneal carcinomatosis. Consequently, CIB1 seems to be a promising prognostic marker and a potential tool for future targeted therapies as well as early diagnostics and follow-up. BioMed Central 2021-11-18 /pmc/articles/PMC8603526/ /pubmed/34794407 http://dx.doi.org/10.1186/s12885-021-08927-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Jacob, Sven
Bösch, Florian
Schoenberg, Markus B.
Pretzsch, Elise
Lampert, Christopher
Haoyu, Ren
Renz, Bernhard W.
Michl, Marlies
Kumbrink, Jörg
Kirchner, Thomas
Werner, Jens
Angele, Martin K.
Neumann, Jens
Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis
title Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis
title_full Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis
title_fullStr Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis
title_full_unstemmed Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis
title_short Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis
title_sort expression of cib1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8603526/
https://www.ncbi.nlm.nih.gov/pubmed/34794407
http://dx.doi.org/10.1186/s12885-021-08927-w
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