Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients

Abstract Immune system plays a dual role in cancer by either targeting or supporting neoplastic cells at various stages of disease, including metastasis. Yet, the exact immune-related transcriptome profiles of primary tumours (PT) and lymph node metastases (LNM) and their evolution during luminal br...

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Autores principales:	Marta Popeda, Aleksandra Markiewicz, Tomasz Stokowy, Jolanta Szade, Magdalena Niemira, Adam Kretowski, Natalia Bednarz-Knoll, Anna J. Zaczek
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e4c0bd97927494ba1f6cc217ca25478
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spelling	oai:doaj.org-article:9e4c0bd97927494ba1f6cc217ca254782021-12-02T13:33:44ZReduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients10.1038/s41598-021-84568-02045-2322https://doaj.org/article/9e4c0bd97927494ba1f6cc217ca254782021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84568-0https://doaj.org/toc/2045-2322Abstract Immune system plays a dual role in cancer by either targeting or supporting neoplastic cells at various stages of disease, including metastasis. Yet, the exact immune-related transcriptome profiles of primary tumours (PT) and lymph node metastases (LNM) and their evolution during luminal breast cancer (BCa) dissemination remain undiscovered. In order to identify the immune-related transcriptome changes that accompany lymphatic spread, we analysed PT-LNM pairs of luminal BCa using NanoString technology. Decrease in complement C3—one of the top-downregulated genes, in LNM was validated at the protein level using immunohistochemistry. Thirty-three of 360 analysed genes were downregulated (9%), whereas only 3 (0.8%) upregulated in LNM when compared to the corresponding PT. In LNM, reduced expression was observed in genes related to innate immunity, particularly to the complement system (C1QB, C1S, C1R, C4B, CFB, C3, SERPING1 and C3AR1). In validation cohort, complement C3 protein was less frequently expressed in LNM than in PT and it was associated with worse prognosis. To conclude, local expression of the complement system components declines during lymphatic spread of non-metastatic luminal BCa, whilst further reduction of tumoral complement C3 in LNM is indicative for poor survival. This points to context-dependent role of complement C3 in BCa dissemination.Marta PopedaAleksandra MarkiewiczTomasz StokowyJolanta SzadeMagdalena NiemiraAdam KretowskiNatalia Bednarz-KnollAnna J. ZaczekNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marta Popeda Aleksandra Markiewicz Tomasz Stokowy Jolanta Szade Magdalena Niemira Adam Kretowski Natalia Bednarz-Knoll Anna J. Zaczek Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients
description	Abstract Immune system plays a dual role in cancer by either targeting or supporting neoplastic cells at various stages of disease, including metastasis. Yet, the exact immune-related transcriptome profiles of primary tumours (PT) and lymph node metastases (LNM) and their evolution during luminal breast cancer (BCa) dissemination remain undiscovered. In order to identify the immune-related transcriptome changes that accompany lymphatic spread, we analysed PT-LNM pairs of luminal BCa using NanoString technology. Decrease in complement C3—one of the top-downregulated genes, in LNM was validated at the protein level using immunohistochemistry. Thirty-three of 360 analysed genes were downregulated (9%), whereas only 3 (0.8%) upregulated in LNM when compared to the corresponding PT. In LNM, reduced expression was observed in genes related to innate immunity, particularly to the complement system (C1QB, C1S, C1R, C4B, CFB, C3, SERPING1 and C3AR1). In validation cohort, complement C3 protein was less frequently expressed in LNM than in PT and it was associated with worse prognosis. To conclude, local expression of the complement system components declines during lymphatic spread of non-metastatic luminal BCa, whilst further reduction of tumoral complement C3 in LNM is indicative for poor survival. This points to context-dependent role of complement C3 in BCa dissemination.
format	article
author	Marta Popeda Aleksandra Markiewicz Tomasz Stokowy Jolanta Szade Magdalena Niemira Adam Kretowski Natalia Bednarz-Knoll Anna J. Zaczek
author_facet	Marta Popeda Aleksandra Markiewicz Tomasz Stokowy Jolanta Szade Magdalena Niemira Adam Kretowski Natalia Bednarz-Knoll Anna J. Zaczek
author_sort	Marta Popeda
title	Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients
title_short	Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients
title_full	Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients
title_fullStr	Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients
title_full_unstemmed	Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients
title_sort	reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9e4c0bd97927494ba1f6cc217ca25478
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Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients

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