Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer

Abstract Gene expression-based subtypes of colorectal cancer have clinical relevance, but the representativeness of primary tumors and the consensus molecular subtypes (CMS) for metastatic cancers is not well known. We investigated the metastatic heterogeneity of CMS. The best approach to subtype tr...

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Autores principales:	Peter W. Eide, Seyed H. Moosavi, Ina A. Eilertsen, Tuva H. Brunsell, Jonas Langerud, Kaja C. G. Berg, Bård I. Røsok, Bjørn A. Bjørnbeth, Arild Nesbakken, Ragnhild A. Lothe, Anita Sveen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/8094865baf5d4bffb26a44258515a35d
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spelling	oai:doaj.org-article:8094865baf5d4bffb26a44258515a35d2021-12-02T17:01:16ZMetastatic heterogeneity of the consensus molecular subtypes of colorectal cancer10.1038/s41525-021-00223-72056-7944https://doaj.org/article/8094865baf5d4bffb26a44258515a35d2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00223-7https://doaj.org/toc/2056-7944Abstract Gene expression-based subtypes of colorectal cancer have clinical relevance, but the representativeness of primary tumors and the consensus molecular subtypes (CMS) for metastatic cancers is not well known. We investigated the metastatic heterogeneity of CMS. The best approach to subtype translation was delineated by comparisons of transcriptomic profiles from 317 primary tumors and 295 liver metastases, including multi-metastatic samples from 45 patients and 14 primary-metastasis sets. Associations were validated in an external data set (n = 618). Projection of metastases onto principal components of primary tumors showed that metastases were depleted of CMS1-immune/CMS3-metabolic signals, enriched for CMS4-mesenchymal/stromal signals, and heavily influenced by the microenvironment. The tailored CMS classifier (available in an updated version of the R package CMScaller) therefore implemented an approach to regress out the liver tissue background. The majority of classified metastases were either CMS2 or CMS4. Nonetheless, subtype switching and inter-metastatic CMS heterogeneity were frequent and increased with sampling intensity. Poor-prognostic value of CMS1/3 metastases was consistent in the context of intra-patient tumor heterogeneity.Peter W. EideSeyed H. MoosaviIna A. EilertsenTuva H. BrunsellJonas LangerudKaja C. G. BergBård I. RøsokBjørn A. BjørnbethArild NesbakkenRagnhild A. LotheAnita SveenNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Peter W. Eide Seyed H. Moosavi Ina A. Eilertsen Tuva H. Brunsell Jonas Langerud Kaja C. G. Berg Bård I. Røsok Bjørn A. Bjørnbeth Arild Nesbakken Ragnhild A. Lothe Anita Sveen Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer
description	Abstract Gene expression-based subtypes of colorectal cancer have clinical relevance, but the representativeness of primary tumors and the consensus molecular subtypes (CMS) for metastatic cancers is not well known. We investigated the metastatic heterogeneity of CMS. The best approach to subtype translation was delineated by comparisons of transcriptomic profiles from 317 primary tumors and 295 liver metastases, including multi-metastatic samples from 45 patients and 14 primary-metastasis sets. Associations were validated in an external data set (n = 618). Projection of metastases onto principal components of primary tumors showed that metastases were depleted of CMS1-immune/CMS3-metabolic signals, enriched for CMS4-mesenchymal/stromal signals, and heavily influenced by the microenvironment. The tailored CMS classifier (available in an updated version of the R package CMScaller) therefore implemented an approach to regress out the liver tissue background. The majority of classified metastases were either CMS2 or CMS4. Nonetheless, subtype switching and inter-metastatic CMS heterogeneity were frequent and increased with sampling intensity. Poor-prognostic value of CMS1/3 metastases was consistent in the context of intra-patient tumor heterogeneity.
format	article
author	Peter W. Eide Seyed H. Moosavi Ina A. Eilertsen Tuva H. Brunsell Jonas Langerud Kaja C. G. Berg Bård I. Røsok Bjørn A. Bjørnbeth Arild Nesbakken Ragnhild A. Lothe Anita Sveen
author_facet	Peter W. Eide Seyed H. Moosavi Ina A. Eilertsen Tuva H. Brunsell Jonas Langerud Kaja C. G. Berg Bård I. Røsok Bjørn A. Bjørnbeth Arild Nesbakken Ragnhild A. Lothe Anita Sveen
author_sort	Peter W. Eide
title	Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer
title_short	Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer
title_full	Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer
title_fullStr	Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer
title_full_unstemmed	Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer
title_sort	metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8094865baf5d4bffb26a44258515a35d
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Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer

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