Proteome biology of primary colorectal carcinoma and corresponding liver metastases

Colorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compa...

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Autores principales:	Matthias Fahrner, Peter Bronsert, Stefan Fichtner-Feigl, Andreas Jud, Oliver Schilling
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Colorectal cancer liver metastases proteomics mass spectrometry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/eb23dc4c5c944ebab5bfba4453dc93a1
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spelling	oai:doaj.org-article:eb23dc4c5c944ebab5bfba4453dc93a12021-11-30T04:14:37ZProteome biology of primary colorectal carcinoma and corresponding liver metastases1476-558610.1016/j.neo.2021.10.005https://doaj.org/article/eb23dc4c5c944ebab5bfba4453dc93a12021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1476558621000907https://doaj.org/toc/1476-5586Colorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compared to non-metastasized CRC patients. The metastasis process and metastasis-promoting factors in patients with CRC are under intensive debate. However, CRC studies investigating the proteome biology are lacking. Formalin-fixed paraffin-embedded (FFPE) tissue specimens provide a valuable resource for comprehensive proteomic studies of a broad variety of clinical malignancies. The presented pilot study compares the proteome of primary CRC and patient-matched CRC-LM. The applied protocol allows a reproducible and straightforward identification and quantification of over 2,600 proteins within the dissected tumorous tissue. Subsequent unsupervised clustering reveals distinct proteome biologies of the primary CRC and the corresponding CRC-LM. Statistical analysis yields multiple differentially abundant proteins in either primary CRC or their corresponding liver metastases. A more detailed analysis of dysregulated biological processes suggests an active immune response in the liver metastases, including several proteins of the complement system. Proteins with structural roles, e.g. cytoskeleton organization or cell junction assembly appear to be less prominent in liver metastases as compared to primary CRC. Immunohistochemistry corroborates proteomic high expression levels of metabolic proteins in CRC-LM. We further assessed how the in vitro inhibition of two in CRC-LM enriched metabolic proteins affected cell proliferation and chemosensitivity. The presented proteomic investigation in a small clinical cohort promotes a more comprehensive understanding of the distinct proteome biology of primary CRC and their corresponding liver metastases.Matthias FahrnerPeter BronsertStefan Fichtner-FeiglAndreas JudOliver SchillingElsevierarticleColorectal cancerliver metastasesproteomicsmass spectrometryNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENNeoplasia: An International Journal for Oncology Research, Vol 23, Iss 12, Pp 1240-1251 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Colorectal cancer liver metastases proteomics mass spectrometry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Colorectal cancer liver metastases proteomics mass spectrometry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Matthias Fahrner Peter Bronsert Stefan Fichtner-Feigl Andreas Jud Oliver Schilling Proteome biology of primary colorectal carcinoma and corresponding liver metastases
description	Colorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compared to non-metastasized CRC patients. The metastasis process and metastasis-promoting factors in patients with CRC are under intensive debate. However, CRC studies investigating the proteome biology are lacking. Formalin-fixed paraffin-embedded (FFPE) tissue specimens provide a valuable resource for comprehensive proteomic studies of a broad variety of clinical malignancies. The presented pilot study compares the proteome of primary CRC and patient-matched CRC-LM. The applied protocol allows a reproducible and straightforward identification and quantification of over 2,600 proteins within the dissected tumorous tissue. Subsequent unsupervised clustering reveals distinct proteome biologies of the primary CRC and the corresponding CRC-LM. Statistical analysis yields multiple differentially abundant proteins in either primary CRC or their corresponding liver metastases. A more detailed analysis of dysregulated biological processes suggests an active immune response in the liver metastases, including several proteins of the complement system. Proteins with structural roles, e.g. cytoskeleton organization or cell junction assembly appear to be less prominent in liver metastases as compared to primary CRC. Immunohistochemistry corroborates proteomic high expression levels of metabolic proteins in CRC-LM. We further assessed how the in vitro inhibition of two in CRC-LM enriched metabolic proteins affected cell proliferation and chemosensitivity. The presented proteomic investigation in a small clinical cohort promotes a more comprehensive understanding of the distinct proteome biology of primary CRC and their corresponding liver metastases.
format	article
author	Matthias Fahrner Peter Bronsert Stefan Fichtner-Feigl Andreas Jud Oliver Schilling
author_facet	Matthias Fahrner Peter Bronsert Stefan Fichtner-Feigl Andreas Jud Oliver Schilling
author_sort	Matthias Fahrner
title	Proteome biology of primary colorectal carcinoma and corresponding liver metastases
title_short	Proteome biology of primary colorectal carcinoma and corresponding liver metastases
title_full	Proteome biology of primary colorectal carcinoma and corresponding liver metastases
title_fullStr	Proteome biology of primary colorectal carcinoma and corresponding liver metastases
title_full_unstemmed	Proteome biology of primary colorectal carcinoma and corresponding liver metastases
title_sort	proteome biology of primary colorectal carcinoma and corresponding liver metastases
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/eb23dc4c5c944ebab5bfba4453dc93a1
work_keys_str_mv	AT matthiasfahrner proteomebiologyofprimarycolorectalcarcinomaandcorrespondinglivermetastases AT peterbronsert proteomebiologyofprimarycolorectalcarcinomaandcorrespondinglivermetastases AT stefanfichtnerfeigl proteomebiologyofprimarycolorectalcarcinomaandcorrespondinglivermetastases AT andreasjud proteomebiologyofprimarycolorectalcarcinomaandcorrespondinglivermetastases AT oliverschilling proteomebiologyofprimarycolorectalcarcinomaandcorrespondinglivermetastases
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Proteome biology of primary colorectal carcinoma and corresponding liver metastases

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