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Exploring the transcriptome of hormone-naive multifocal prostate cancer and matched lymph node metastases
BACKGROUND: The current inability to predict whether a primary prostate cancer (PC) will progress to metastatic disease leads to overtreatment of indolent PCs as well as undertreatment of aggressive PCs. Here, we explored the transcriptional changes associated with metastatic progression of multifoc...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288156/ https://www.ncbi.nlm.nih.gov/pubmed/30449885 http://dx.doi.org/10.1038/s41416-018-0321-5 |
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author | Schmidt, Linnéa Møller, Mia Haldrup, Christa Strand, Siri H. Vang, Søren Hedegaard, Jakob Høyer, Søren Borre, Michael Ørntoft, Torben Sørensen, Karina Dalsgaard |
author_facet | Schmidt, Linnéa Møller, Mia Haldrup, Christa Strand, Siri H. Vang, Søren Hedegaard, Jakob Høyer, Søren Borre, Michael Ørntoft, Torben Sørensen, Karina Dalsgaard |
author_sort | Schmidt, Linnéa |
collection | PubMed |
description | BACKGROUND: The current inability to predict whether a primary prostate cancer (PC) will progress to metastatic disease leads to overtreatment of indolent PCs as well as undertreatment of aggressive PCs. Here, we explored the transcriptional changes associated with metastatic progression of multifocal hormone-naive PC. METHODS: Using total RNA-sequencing, we analysed laser micro-dissected primary PC foci (n = 23), adjacent normal prostate tissue samples (n = 23) and lymph node metastases (n = 9) from ten hormone-naive PC patients. Genes important for PC progression were identified using differential gene expression and clustering analysis. From these, two multi-gene-based expression signatures (models) were developed, and their prognostic potential was evaluated using Cox-regression and Kaplan–Meier analyses in three independent radical prostatectomy (RP) cohorts (>650 patients). RESULTS: We identified several novel PC-associated transcripts deregulated during PC progression, and these transcripts were used to develop two novel gene-expression-based prognostic models. The models showed independent prognostic potential in three RP cohorts (n = 405, n = 107 and n = 91), using biochemical recurrence after RP as the primary clinical endpoint. CONCLUSIONS: We identified several transcripts deregulated during PC progression and developed two new prognostic models for PC risk stratification, each of which showed independent prognostic value beyond routine clinicopathological factors in three independent RP cohorts. |
format | Online Article Text |
id | pubmed-6288156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62881562019-06-21 Exploring the transcriptome of hormone-naive multifocal prostate cancer and matched lymph node metastases Schmidt, Linnéa Møller, Mia Haldrup, Christa Strand, Siri H. Vang, Søren Hedegaard, Jakob Høyer, Søren Borre, Michael Ørntoft, Torben Sørensen, Karina Dalsgaard Br J Cancer Article BACKGROUND: The current inability to predict whether a primary prostate cancer (PC) will progress to metastatic disease leads to overtreatment of indolent PCs as well as undertreatment of aggressive PCs. Here, we explored the transcriptional changes associated with metastatic progression of multifocal hormone-naive PC. METHODS: Using total RNA-sequencing, we analysed laser micro-dissected primary PC foci (n = 23), adjacent normal prostate tissue samples (n = 23) and lymph node metastases (n = 9) from ten hormone-naive PC patients. Genes important for PC progression were identified using differential gene expression and clustering analysis. From these, two multi-gene-based expression signatures (models) were developed, and their prognostic potential was evaluated using Cox-regression and Kaplan–Meier analyses in three independent radical prostatectomy (RP) cohorts (>650 patients). RESULTS: We identified several novel PC-associated transcripts deregulated during PC progression, and these transcripts were used to develop two novel gene-expression-based prognostic models. The models showed independent prognostic potential in three RP cohorts (n = 405, n = 107 and n = 91), using biochemical recurrence after RP as the primary clinical endpoint. CONCLUSIONS: We identified several transcripts deregulated during PC progression and developed two new prognostic models for PC risk stratification, each of which showed independent prognostic value beyond routine clinicopathological factors in three independent RP cohorts. Nature Publishing Group UK 2018-11-19 2018-12-11 /pmc/articles/PMC6288156/ /pubmed/30449885 http://dx.doi.org/10.1038/s41416-018-0321-5 Text en © The Author(s) 2018 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Schmidt, Linnéa Møller, Mia Haldrup, Christa Strand, Siri H. Vang, Søren Hedegaard, Jakob Høyer, Søren Borre, Michael Ørntoft, Torben Sørensen, Karina Dalsgaard Exploring the transcriptome of hormone-naive multifocal prostate cancer and matched lymph node metastases |
title | Exploring the transcriptome of hormone-naive multifocal prostate cancer and matched lymph node metastases |
title_full | Exploring the transcriptome of hormone-naive multifocal prostate cancer and matched lymph node metastases |
title_fullStr | Exploring the transcriptome of hormone-naive multifocal prostate cancer and matched lymph node metastases |
title_full_unstemmed | Exploring the transcriptome of hormone-naive multifocal prostate cancer and matched lymph node metastases |
title_short | Exploring the transcriptome of hormone-naive multifocal prostate cancer and matched lymph node metastases |
title_sort | exploring the transcriptome of hormone-naive multifocal prostate cancer and matched lymph node metastases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288156/ https://www.ncbi.nlm.nih.gov/pubmed/30449885 http://dx.doi.org/10.1038/s41416-018-0321-5 |
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