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

Abstract 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 personalize...

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Autores principales: Sven Jacob, Florian Bösch, Markus B. Schoenberg, Elise Pretzsch, Christopher Lampert, Ren Haoyu, Bernhard W. Renz, Marlies Michl, Jörg Kumbrink, Thomas Kirchner, Jens Werner, Martin K. Angele, Jens Neumann
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Publicado: BMC 2021
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spelling oai:doaj.org-article:80c7cc8532c74acdb1342db764e9e6552021-11-21T12:30:08ZExpression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis10.1186/s12885-021-08927-w1471-2407https://doaj.org/article/80c7cc8532c74acdb1342db764e9e6552021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08927-whttps://doaj.org/toc/1471-2407Abstract 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.Sven JacobFlorian BöschMarkus B. SchoenbergElise PretzschChristopher LampertRen HaoyuBernhard W. RenzMarlies MichlJörg KumbrinkThomas KirchnerJens WernerMartin K. AngeleJens NeumannBMCarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Sven Jacob
Florian Bösch
Markus B. Schoenberg
Elise Pretzsch
Christopher Lampert
Ren Haoyu
Bernhard W. Renz
Marlies Michl
Jörg Kumbrink
Thomas Kirchner
Jens Werner
Martin K. Angele
Jens Neumann
Expression of CIB1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis
description Abstract 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.
format article
author Sven Jacob
Florian Bösch
Markus B. Schoenberg
Elise Pretzsch
Christopher Lampert
Ren Haoyu
Bernhard W. Renz
Marlies Michl
Jörg Kumbrink
Thomas Kirchner
Jens Werner
Martin K. Angele
Jens Neumann
author_facet Sven Jacob
Florian Bösch
Markus B. Schoenberg
Elise Pretzsch
Christopher Lampert
Ren Haoyu
Bernhard W. Renz
Marlies Michl
Jörg Kumbrink
Thomas Kirchner
Jens Werner
Martin K. Angele
Jens Neumann
author_sort Sven Jacob
title 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_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_sort expression of cib1 correlates with colorectal liver metastases but not with peritoneal carcinomatosis
publisher BMC
publishDate 2021
url https://doaj.org/article/80c7cc8532c74acdb1342db764e9e655
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