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NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer

The role of circulating tumor cells (CTCs), tumor microenvironment (TME), and the immune system in the formation of metastasis is evident, yet the details of their interactions remain unknown. This study aimed at exploring the immunotranscriptome of primary tumors associated with the status of CTCs...

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Autores principales: Popeda, Marta, Stokowy, Tomasz, Bednarz-Knoll, Natalia, Jurek, Anna, Niemira, Magdalena, Bielska, Agnieszka, Kretowski, Adam, Kalinowski, Leszek, Szade, Jolanta, Markiewicz, Aleksandra, Zaczek, Anna J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966426/
https://www.ncbi.nlm.nih.gov/pubmed/31817685
http://dx.doi.org/10.3390/cancers11121961
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author Popeda, Marta
Stokowy, Tomasz
Bednarz-Knoll, Natalia
Jurek, Anna
Niemira, Magdalena
Bielska, Agnieszka
Kretowski, Adam
Kalinowski, Leszek
Szade, Jolanta
Markiewicz, Aleksandra
Zaczek, Anna J.
author_facet Popeda, Marta
Stokowy, Tomasz
Bednarz-Knoll, Natalia
Jurek, Anna
Niemira, Magdalena
Bielska, Agnieszka
Kretowski, Adam
Kalinowski, Leszek
Szade, Jolanta
Markiewicz, Aleksandra
Zaczek, Anna J.
author_sort Popeda, Marta
collection PubMed
description The role of circulating tumor cells (CTCs), tumor microenvironment (TME), and the immune system in the formation of metastasis is evident, yet the details of their interactions remain unknown. This study aimed at exploring the immunotranscriptome of primary tumors associated with the status of CTCs in breast cancer (BCa) patients. The expression of 730 immune-related genes in formalin-fixed paraffin-embedded samples was analyzed using the multigenomic NanoString technology and correlated with the presence and the phenotype of CTCs. Upregulation of 37 genes and downregulation of 1 gene were observed in patients characterized by a mesenchymal phenotype of CTCs when compared to patients with epithelial CTCs. The upregulated genes were involved in NF-kappa B signaling and in the production of type I interferons. The clinical significance of the differentially expressed genes was evaluated using The Cancer Genome Atlas (TCGA) data of a breast invasive carcinoma (BRCA) cohort. Five of the upregulated genes—PSMD7, C2, IFNAR1, CD84, and CYLD—were independent prognostic factors in terms of overall and disease-free survival. To conclude, our data identify a group of genes that are upregulated in BCa patients with mesenchymal CTCs and reveal their prognostic potential, thus indicating that they merit further investigation.
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spelling pubmed-69664262020-01-27 NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer Popeda, Marta Stokowy, Tomasz Bednarz-Knoll, Natalia Jurek, Anna Niemira, Magdalena Bielska, Agnieszka Kretowski, Adam Kalinowski, Leszek Szade, Jolanta Markiewicz, Aleksandra Zaczek, Anna J. Cancers (Basel) Article The role of circulating tumor cells (CTCs), tumor microenvironment (TME), and the immune system in the formation of metastasis is evident, yet the details of their interactions remain unknown. This study aimed at exploring the immunotranscriptome of primary tumors associated with the status of CTCs in breast cancer (BCa) patients. The expression of 730 immune-related genes in formalin-fixed paraffin-embedded samples was analyzed using the multigenomic NanoString technology and correlated with the presence and the phenotype of CTCs. Upregulation of 37 genes and downregulation of 1 gene were observed in patients characterized by a mesenchymal phenotype of CTCs when compared to patients with epithelial CTCs. The upregulated genes were involved in NF-kappa B signaling and in the production of type I interferons. The clinical significance of the differentially expressed genes was evaluated using The Cancer Genome Atlas (TCGA) data of a breast invasive carcinoma (BRCA) cohort. Five of the upregulated genes—PSMD7, C2, IFNAR1, CD84, and CYLD—were independent prognostic factors in terms of overall and disease-free survival. To conclude, our data identify a group of genes that are upregulated in BCa patients with mesenchymal CTCs and reveal their prognostic potential, thus indicating that they merit further investigation. MDPI 2019-12-06 /pmc/articles/PMC6966426/ /pubmed/31817685 http://dx.doi.org/10.3390/cancers11121961 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Popeda, Marta
Stokowy, Tomasz
Bednarz-Knoll, Natalia
Jurek, Anna
Niemira, Magdalena
Bielska, Agnieszka
Kretowski, Adam
Kalinowski, Leszek
Szade, Jolanta
Markiewicz, Aleksandra
Zaczek, Anna J.
NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer
title NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer
title_full NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer
title_fullStr NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer
title_full_unstemmed NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer
title_short NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer
title_sort nf-kappa b signaling-related signatures are connected with the mesenchymal phenotype of circulating tumor cells in non-metastatic breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966426/
https://www.ncbi.nlm.nih.gov/pubmed/31817685
http://dx.doi.org/10.3390/cancers11121961
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