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Prognostic microRNAs modulate the RHO adhesion pathway: A potential therapeutic target in undifferentiated pleomorphic sarcomas

A common and aggressive subtype of soft-tissue sarcoma, undifferentiated pleomorphic sarcoma (UPS) was examined to determine the role of micro-RNAs (miRNAs) in modulating distant metastasis. Following histopathologic review, 110 fresh frozen clinically annotated UPS samples were divided into two ind...

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Autores principales: Wong, Philip, Hui, Angela, Su, Jie, Yue, Shijun, Haibe-Kains, Benjamin, Gokgoz, Nalan, Xu, Wei, Bruce, Jeff, Williams, Justin, Catton, Charles, Wunder, Jay S., Andrulis, Irene L., Gladdy, Rebecca, Dickson, Brendan, O'Sullivan, Brian, Liu, Fei-Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770761/
https://www.ncbi.nlm.nih.gov/pubmed/25970788
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author Wong, Philip
Hui, Angela
Su, Jie
Yue, Shijun
Haibe-Kains, Benjamin
Gokgoz, Nalan
Xu, Wei
Bruce, Jeff
Williams, Justin
Catton, Charles
Wunder, Jay S.
Andrulis, Irene L.
Gladdy, Rebecca
Dickson, Brendan
O'Sullivan, Brian
Liu, Fei-Fei
author_facet Wong, Philip
Hui, Angela
Su, Jie
Yue, Shijun
Haibe-Kains, Benjamin
Gokgoz, Nalan
Xu, Wei
Bruce, Jeff
Williams, Justin
Catton, Charles
Wunder, Jay S.
Andrulis, Irene L.
Gladdy, Rebecca
Dickson, Brendan
O'Sullivan, Brian
Liu, Fei-Fei
author_sort Wong, Philip
collection PubMed
description A common and aggressive subtype of soft-tissue sarcoma, undifferentiated pleomorphic sarcoma (UPS) was examined to determine the role of micro-RNAs (miRNAs) in modulating distant metastasis. Following histopathologic review, 110 fresh frozen clinically annotated UPS samples were divided into two independent cohorts for Training (42 patients), and Validation (68 patients) analyses. Global miRNA profiling on the Training Set and functional analysis in vitro suggested that miRNA-138 and its downstream RHO-ROCK cell adhesion pathway was a convergent target of miRNAs associated with the development of metastasis. A six-miRNA signature set prognostic of distant metastasis-free survival (DMFS) was developed from Training Set miRNA expression values. Using the six-miRNA signature, patients were successfully categorized into high- and low-risk groups for DMFS in an independent Validation Set, with a hazard ratio (HR) of 2.25 (p = 0.048). After adjusting for other known prognostic variables such as age, gender, tumor grade, size, depth, and treatment with radiotherapy, the six-miRNA signature retained prognostic value with a HR of 3.46 (p < 0.001). A prognostic miRNA biomarker for clinical validation was thus identified along with a functional pathway that modulates UPS metastatic phenotype.
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spelling pubmed-47707612016-03-21 Prognostic microRNAs modulate the RHO adhesion pathway: A potential therapeutic target in undifferentiated pleomorphic sarcomas Wong, Philip Hui, Angela Su, Jie Yue, Shijun Haibe-Kains, Benjamin Gokgoz, Nalan Xu, Wei Bruce, Jeff Williams, Justin Catton, Charles Wunder, Jay S. Andrulis, Irene L. Gladdy, Rebecca Dickson, Brendan O'Sullivan, Brian Liu, Fei-Fei Oncotarget Research Paper A common and aggressive subtype of soft-tissue sarcoma, undifferentiated pleomorphic sarcoma (UPS) was examined to determine the role of micro-RNAs (miRNAs) in modulating distant metastasis. Following histopathologic review, 110 fresh frozen clinically annotated UPS samples were divided into two independent cohorts for Training (42 patients), and Validation (68 patients) analyses. Global miRNA profiling on the Training Set and functional analysis in vitro suggested that miRNA-138 and its downstream RHO-ROCK cell adhesion pathway was a convergent target of miRNAs associated with the development of metastasis. A six-miRNA signature set prognostic of distant metastasis-free survival (DMFS) was developed from Training Set miRNA expression values. Using the six-miRNA signature, patients were successfully categorized into high- and low-risk groups for DMFS in an independent Validation Set, with a hazard ratio (HR) of 2.25 (p = 0.048). After adjusting for other known prognostic variables such as age, gender, tumor grade, size, depth, and treatment with radiotherapy, the six-miRNA signature retained prognostic value with a HR of 3.46 (p < 0.001). A prognostic miRNA biomarker for clinical validation was thus identified along with a functional pathway that modulates UPS metastatic phenotype. Impact Journals LLC 2015-04-23 /pmc/articles/PMC4770761/ /pubmed/25970788 Text en Copyright: © 2015 Wong et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Wong, Philip
Hui, Angela
Su, Jie
Yue, Shijun
Haibe-Kains, Benjamin
Gokgoz, Nalan
Xu, Wei
Bruce, Jeff
Williams, Justin
Catton, Charles
Wunder, Jay S.
Andrulis, Irene L.
Gladdy, Rebecca
Dickson, Brendan
O'Sullivan, Brian
Liu, Fei-Fei
Prognostic microRNAs modulate the RHO adhesion pathway: A potential therapeutic target in undifferentiated pleomorphic sarcomas
title Prognostic microRNAs modulate the RHO adhesion pathway: A potential therapeutic target in undifferentiated pleomorphic sarcomas
title_full Prognostic microRNAs modulate the RHO adhesion pathway: A potential therapeutic target in undifferentiated pleomorphic sarcomas
title_fullStr Prognostic microRNAs modulate the RHO adhesion pathway: A potential therapeutic target in undifferentiated pleomorphic sarcomas
title_full_unstemmed Prognostic microRNAs modulate the RHO adhesion pathway: A potential therapeutic target in undifferentiated pleomorphic sarcomas
title_short Prognostic microRNAs modulate the RHO adhesion pathway: A potential therapeutic target in undifferentiated pleomorphic sarcomas
title_sort prognostic micrornas modulate the rho adhesion pathway: a potential therapeutic target in undifferentiated pleomorphic sarcomas
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770761/
https://www.ncbi.nlm.nih.gov/pubmed/25970788
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