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Stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a markedly heterogeneous disease in many aspects, including the tumour microenvironment. Our previous study showed the importance of the tumour microenvironment in ccRCC xeno-transplant success rates. In order to better understand the potential...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119074/ https://www.ncbi.nlm.nih.gov/pubmed/32245446 http://dx.doi.org/10.1186/s12885-020-06733-4 |
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author | Yoon, Ju-Yoon Gedye, Craig Paterson, Joshua Ailles, Laurie |
author_facet | Yoon, Ju-Yoon Gedye, Craig Paterson, Joshua Ailles, Laurie |
author_sort | Yoon, Ju-Yoon |
collection | PubMed |
description | BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a markedly heterogeneous disease in many aspects, including the tumour microenvironment. Our previous study showed the importance of the tumour microenvironment in ccRCC xeno-transplant success rates. In order to better understand the potential relationship between TICs and the immune microenvironment, we employed a multi-modal approach, examining RNA and protein expression (flow cytometry, immunohistochemistry). METHODS: We first examined the gene expression pattern of 18 stem/progenitor marker genes in the cancer genome atlas (TCGA) ccRCC cohort. Flow cytometry was next employed to examine lineage-specific expression levels of stem/progenitor markers and immune population makeup in six, disaggregated, primary ccRCC specimens. Immunohistochemistry was performed on a commercial ccRCC tissue microarray (TMA). RESULTS: The 18 genes differed with respect to their correlation patterns with one another and to their prognostic significance. By flow cytometry, correlating expression frequency of 12 stem/progenitor markers and CD10 resulted in two clusters—one with CD10 (marker of proximal tubular differentiation), and second cluster containing mostly mesenchymal stem cell (MSC) markers, including CD146. In turn, these clusters differed with respect to their correlation with different CD45(+) lineage markers and their expression of immune checkpoint pathway proteins. To confirm these findings, four stem/progenitor marker expression patterns were compared with CD4, CD8 and CD20 in a ccRCC TMA which showed a number of similar trends with respect to frequency of the different tumour-infiltrating leukocytes. CONCLUSION: Taken together, we observed heterogeneous but patterned expression levels of different stem/progenitor markers. Our results suggest a non-random relationship between their expression patterns with the immune microenvironment populations in ccRCC. |
format | Online Article Text |
id | pubmed-7119074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-71190742020-04-07 Stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored Yoon, Ju-Yoon Gedye, Craig Paterson, Joshua Ailles, Laurie BMC Cancer Research Article BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a markedly heterogeneous disease in many aspects, including the tumour microenvironment. Our previous study showed the importance of the tumour microenvironment in ccRCC xeno-transplant success rates. In order to better understand the potential relationship between TICs and the immune microenvironment, we employed a multi-modal approach, examining RNA and protein expression (flow cytometry, immunohistochemistry). METHODS: We first examined the gene expression pattern of 18 stem/progenitor marker genes in the cancer genome atlas (TCGA) ccRCC cohort. Flow cytometry was next employed to examine lineage-specific expression levels of stem/progenitor markers and immune population makeup in six, disaggregated, primary ccRCC specimens. Immunohistochemistry was performed on a commercial ccRCC tissue microarray (TMA). RESULTS: The 18 genes differed with respect to their correlation patterns with one another and to their prognostic significance. By flow cytometry, correlating expression frequency of 12 stem/progenitor markers and CD10 resulted in two clusters—one with CD10 (marker of proximal tubular differentiation), and second cluster containing mostly mesenchymal stem cell (MSC) markers, including CD146. In turn, these clusters differed with respect to their correlation with different CD45(+) lineage markers and their expression of immune checkpoint pathway proteins. To confirm these findings, four stem/progenitor marker expression patterns were compared with CD4, CD8 and CD20 in a ccRCC TMA which showed a number of similar trends with respect to frequency of the different tumour-infiltrating leukocytes. CONCLUSION: Taken together, we observed heterogeneous but patterned expression levels of different stem/progenitor markers. Our results suggest a non-random relationship between their expression patterns with the immune microenvironment populations in ccRCC. BioMed Central 2020-04-03 /pmc/articles/PMC7119074/ /pubmed/32245446 http://dx.doi.org/10.1186/s12885-020-06733-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Yoon, Ju-Yoon Gedye, Craig Paterson, Joshua Ailles, Laurie Stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored |
title | Stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored |
title_full | Stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored |
title_fullStr | Stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored |
title_full_unstemmed | Stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored |
title_short | Stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored |
title_sort | stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119074/ https://www.ncbi.nlm.nih.gov/pubmed/32245446 http://dx.doi.org/10.1186/s12885-020-06733-4 |
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