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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Veröffentlicht in: | Cancers 2019-12, Vol.11 (12), p.1961 |
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creator | Popeda, Marta Stokowy, Tomasz Bednarz-Knoll, Natalia Jurek, Anna Niemira, Magdalena Bielska, Agnieszka Kretowski, Adam Kalinowski, Leszek Szade, Jolanta Markiewicz, Aleksandra Zaczek, Anna J |
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-
,
,
, and
-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. |
doi_str_mv | 10.3390/cancers11121961 |
format | Article |
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,
,
, and
-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.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers11121961</identifier><identifier>PMID: 31817685</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Breast cancer ; Gene expression ; Genomes ; Genotype & phenotype ; Immune system ; Interferon ; Invasiveness ; Medical prognosis ; Mesenchyme ; Metastases ; Metastasis ; NF-κB protein ; Paraffin ; Phenotypes ; Tumor cells ; Tumor microenvironment ; Tumors</subject><ispartof>Cancers, 2019-12, Vol.11 (12), p.1961</ispartof><rights>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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-23553c6a5c21e9cbc81c170c9aec2d50c36c3b4f9f306a0f95f54ed96034edc43</citedby><cites>FETCH-LOGICAL-c421t-23553c6a5c21e9cbc81c170c9aec2d50c36c3b4f9f306a0f95f54ed96034edc43</cites><orcidid>0000-0003-1482-6068 ; 0000-0002-4522-4978 ; 0000-0001-9506-942X ; 0000-0002-4596-4837 ; 0000-0002-0701-4961 ; 0000-0003-0017-8338 ; 0000-0003-4590-4698 ; 0000-0001-5886-4854</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966426/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966426/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31817685$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Popeda, Marta</creatorcontrib><creatorcontrib>Stokowy, Tomasz</creatorcontrib><creatorcontrib>Bednarz-Knoll, Natalia</creatorcontrib><creatorcontrib>Jurek, Anna</creatorcontrib><creatorcontrib>Niemira, Magdalena</creatorcontrib><creatorcontrib>Bielska, Agnieszka</creatorcontrib><creatorcontrib>Kretowski, Adam</creatorcontrib><creatorcontrib>Kalinowski, Leszek</creatorcontrib><creatorcontrib>Szade, Jolanta</creatorcontrib><creatorcontrib>Markiewicz, Aleksandra</creatorcontrib><creatorcontrib>Zaczek, Anna J</creatorcontrib><title>NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><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-
,
,
, and
-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.</description><subject>Breast cancer</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Immune system</subject><subject>Interferon</subject><subject>Invasiveness</subject><subject>Medical prognosis</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>NF-κB protein</subject><subject>Paraffin</subject><subject>Phenotypes</subject><subject>Tumor cells</subject><subject>Tumor microenvironment</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdUU1v1DAQjRCIVqVnbsgSFy6h_k58QWojCkhtQVDOkXd2sklJ7NR2QPsr-Mt42VKV-jKjec9v_PyK4iWjb4Uw9ASsAwyRMcaZ0exJcchpxUutjXz6oD8ojmO8ofkIwSpdPS8OBKtzV6vD4vfVefnDzrMlZ-TbsHF2HNym_IqjTbjeT9ISMJLTgKTxziHsgF9D6knqkVxiRAf9drIj-dKj82k7I_EdaYYAS1bJcuR6mXwgDY5jJIMjV96Vl5hsTBkGchYwt6T56-ZF8ayzY8Tju3pUfD9_f918LC8-f_jUnF6UIDlLJRdKCdBWAWdoYAU1A1ZRMBaBrxUFoUGsZGc6QbWlnVGdkrg2mopcQIqj4t1ed15WU56gS8GO7RyGyYZt6-3Q_o-4oW83_merjdaS6yzw5k4g-NsFY2qnIUK2aB36JbZccCErLeRu1-tH1Bu_hPzVmaVkpYysVZ1ZJ3sWBB9jwO7-MYy2u7zbR3nnG68eerjn_0tX_AGwyKmz</recordid><startdate>20191206</startdate><enddate>20191206</enddate><creator>Popeda, Marta</creator><creator>Stokowy, Tomasz</creator><creator>Bednarz-Knoll, Natalia</creator><creator>Jurek, Anna</creator><creator>Niemira, Magdalena</creator><creator>Bielska, Agnieszka</creator><creator>Kretowski, Adam</creator><creator>Kalinowski, Leszek</creator><creator>Szade, Jolanta</creator><creator>Markiewicz, Aleksandra</creator><creator>Zaczek, Anna J</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1482-6068</orcidid><orcidid>https://orcid.org/0000-0002-4522-4978</orcidid><orcidid>https://orcid.org/0000-0001-9506-942X</orcidid><orcidid>https://orcid.org/0000-0002-4596-4837</orcidid><orcidid>https://orcid.org/0000-0002-0701-4961</orcidid><orcidid>https://orcid.org/0000-0003-0017-8338</orcidid><orcidid>https://orcid.org/0000-0003-4590-4698</orcidid><orcidid>https://orcid.org/0000-0001-5886-4854</orcidid></search><sort><creationdate>20191206</creationdate><title>NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-23553c6a5c21e9cbc81c170c9aec2d50c36c3b4f9f306a0f95f54ed96034edc43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Breast cancer</topic><topic>Gene expression</topic><topic>Genomes</topic><topic>Genotype & phenotype</topic><topic>Immune system</topic><topic>Interferon</topic><topic>Invasiveness</topic><topic>Medical prognosis</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>NF-κB protein</topic><topic>Paraffin</topic><topic>Phenotypes</topic><topic>Tumor cells</topic><topic>Tumor microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Popeda, Marta</creatorcontrib><creatorcontrib>Stokowy, Tomasz</creatorcontrib><creatorcontrib>Bednarz-Knoll, Natalia</creatorcontrib><creatorcontrib>Jurek, Anna</creatorcontrib><creatorcontrib>Niemira, Magdalena</creatorcontrib><creatorcontrib>Bielska, Agnieszka</creatorcontrib><creatorcontrib>Kretowski, Adam</creatorcontrib><creatorcontrib>Kalinowski, Leszek</creatorcontrib><creatorcontrib>Szade, Jolanta</creatorcontrib><creatorcontrib>Markiewicz, Aleksandra</creatorcontrib><creatorcontrib>Zaczek, Anna J</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Popeda, Marta</au><au>Stokowy, Tomasz</au><au>Bednarz-Knoll, Natalia</au><au>Jurek, Anna</au><au>Niemira, Magdalena</au><au>Bielska, Agnieszka</au><au>Kretowski, Adam</au><au>Kalinowski, Leszek</au><au>Szade, Jolanta</au><au>Markiewicz, Aleksandra</au><au>Zaczek, Anna J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2019-12-06</date><risdate>2019</risdate><volume>11</volume><issue>12</issue><spage>1961</spage><pages>1961-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>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-
,
,
, and
-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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31817685</pmid><doi>10.3390/cancers11121961</doi><orcidid>https://orcid.org/0000-0003-1482-6068</orcidid><orcidid>https://orcid.org/0000-0002-4522-4978</orcidid><orcidid>https://orcid.org/0000-0001-9506-942X</orcidid><orcidid>https://orcid.org/0000-0002-4596-4837</orcidid><orcidid>https://orcid.org/0000-0002-0701-4961</orcidid><orcidid>https://orcid.org/0000-0003-0017-8338</orcidid><orcidid>https://orcid.org/0000-0003-4590-4698</orcidid><orcidid>https://orcid.org/0000-0001-5886-4854</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Breast cancer Gene expression Genomes Genotype & phenotype Immune system Interferon Invasiveness Medical prognosis Mesenchyme Metastases Metastasis NF-κB protein Paraffin Phenotypes Tumor cells Tumor microenvironment Tumors |
title | NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer |
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