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A multiomics disease progression signature of low-risk ccRCC

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Identification of ccRCC likely to progress, despite an apparent low risk at the time of surgery, represents a key clinical issue. From a cohort of adult ccRCC patients (n = 443), we selected low-risk tumors progressing within a...

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Autores principales: Strauss, Philipp, Rivedal, Mariell, Scherer, Andreas, Eikrem, Øystein, Nakken, Sigrid, Beisland, Christian, Bostad, Leif, Flatberg, Arnar, Skandalou, Eleni, Beisvåg, Vidar, Furriol, Jessica, Marti, Hans-Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356046/
https://www.ncbi.nlm.nih.gov/pubmed/35931808
http://dx.doi.org/10.1038/s41598-022-17755-2
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author Strauss, Philipp
Rivedal, Mariell
Scherer, Andreas
Eikrem, Øystein
Nakken, Sigrid
Beisland, Christian
Bostad, Leif
Flatberg, Arnar
Skandalou, Eleni
Beisvåg, Vidar
Furriol, Jessica
Marti, Hans-Peter
author_facet Strauss, Philipp
Rivedal, Mariell
Scherer, Andreas
Eikrem, Øystein
Nakken, Sigrid
Beisland, Christian
Bostad, Leif
Flatberg, Arnar
Skandalou, Eleni
Beisvåg, Vidar
Furriol, Jessica
Marti, Hans-Peter
author_sort Strauss, Philipp
collection PubMed
description Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Identification of ccRCC likely to progress, despite an apparent low risk at the time of surgery, represents a key clinical issue. From a cohort of adult ccRCC patients (n = 443), we selected low-risk tumors progressing within a 5-years average follow-up (progressors: P, n = 8) and non-progressing (NP) tumors (n = 16). Transcriptome sequencing, miRNA sequencing and proteomics were performed on tissues obtained at surgery. We identified 151 proteins, 1167 mRNAs and 63 miRNAs differentially expressed in P compared to NP low-risk tumors. Pathway analysis demonstrated overrepresentation of proteins related to “LXR/RXR and FXR/RXR Activation”, “Acute Phase Response Signaling” in NP compared to P samples. Integrating mRNA, miRNA and proteomic data, we developed a 10-component classifier including two proteins, three genes and five miRNAs, effectively differentiating P and NP ccRCC and capturing underlying biological differences, potentially useful to identify “low-risk” patients requiring closer surveillance and treatment adjustments. Key results were validated by immunohistochemistry, qPCR and data from publicly available databases. Our work suggests that LXR, FXR and macrophage activation pathways could be critically involved in the inhibition of the progression of low-risk ccRCC. Furthermore, a 10-component classifier could support an early identification of apparently low-risk ccRCC patients.
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spelling pubmed-93560462022-08-07 A multiomics disease progression signature of low-risk ccRCC Strauss, Philipp Rivedal, Mariell Scherer, Andreas Eikrem, Øystein Nakken, Sigrid Beisland, Christian Bostad, Leif Flatberg, Arnar Skandalou, Eleni Beisvåg, Vidar Furriol, Jessica Marti, Hans-Peter Sci Rep Article Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Identification of ccRCC likely to progress, despite an apparent low risk at the time of surgery, represents a key clinical issue. From a cohort of adult ccRCC patients (n = 443), we selected low-risk tumors progressing within a 5-years average follow-up (progressors: P, n = 8) and non-progressing (NP) tumors (n = 16). Transcriptome sequencing, miRNA sequencing and proteomics were performed on tissues obtained at surgery. We identified 151 proteins, 1167 mRNAs and 63 miRNAs differentially expressed in P compared to NP low-risk tumors. Pathway analysis demonstrated overrepresentation of proteins related to “LXR/RXR and FXR/RXR Activation”, “Acute Phase Response Signaling” in NP compared to P samples. Integrating mRNA, miRNA and proteomic data, we developed a 10-component classifier including two proteins, three genes and five miRNAs, effectively differentiating P and NP ccRCC and capturing underlying biological differences, potentially useful to identify “low-risk” patients requiring closer surveillance and treatment adjustments. Key results were validated by immunohistochemistry, qPCR and data from publicly available databases. Our work suggests that LXR, FXR and macrophage activation pathways could be critically involved in the inhibition of the progression of low-risk ccRCC. Furthermore, a 10-component classifier could support an early identification of apparently low-risk ccRCC patients. Nature Publishing Group UK 2022-08-05 /pmc/articles/PMC9356046/ /pubmed/35931808 http://dx.doi.org/10.1038/s41598-022-17755-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Strauss, Philipp
Rivedal, Mariell
Scherer, Andreas
Eikrem, Øystein
Nakken, Sigrid
Beisland, Christian
Bostad, Leif
Flatberg, Arnar
Skandalou, Eleni
Beisvåg, Vidar
Furriol, Jessica
Marti, Hans-Peter
A multiomics disease progression signature of low-risk ccRCC
title A multiomics disease progression signature of low-risk ccRCC
title_full A multiomics disease progression signature of low-risk ccRCC
title_fullStr A multiomics disease progression signature of low-risk ccRCC
title_full_unstemmed A multiomics disease progression signature of low-risk ccRCC
title_short A multiomics disease progression signature of low-risk ccRCC
title_sort multiomics disease progression signature of low-risk ccrcc
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356046/
https://www.ncbi.nlm.nih.gov/pubmed/35931808
http://dx.doi.org/10.1038/s41598-022-17755-2
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