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Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread

High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread type...

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Autores principales: Bachmayr-Heyda, Anna, Auer, Katharina, Sukhbaatar, Nyamdelger, Aust, Stefanie, Deycmar, Simon, Reiner, Agnes T., Polterauer, Stephan, Dekan, Sabine, Pils, Dietmar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129959/
https://www.ncbi.nlm.nih.gov/pubmed/27172797
http://dx.doi.org/10.18632/oncotarget.9243
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author Bachmayr-Heyda, Anna
Auer, Katharina
Sukhbaatar, Nyamdelger
Aust, Stefanie
Deycmar, Simon
Reiner, Agnes T.
Polterauer, Stephan
Dekan, Sabine
Pils, Dietmar
author_facet Bachmayr-Heyda, Anna
Auer, Katharina
Sukhbaatar, Nyamdelger
Aust, Stefanie
Deycmar, Simon
Reiner, Agnes T.
Polterauer, Stephan
Dekan, Sabine
Pils, Dietmar
author_sort Bachmayr-Heyda, Anna
collection PubMed
description High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors. 23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed. Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer.
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spelling pubmed-51299592016-12-11 Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread Bachmayr-Heyda, Anna Auer, Katharina Sukhbaatar, Nyamdelger Aust, Stefanie Deycmar, Simon Reiner, Agnes T. Polterauer, Stephan Dekan, Sabine Pils, Dietmar Oncotarget Research Paper High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors. 23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed. Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer. Impact Journals LLC 2016-05-09 /pmc/articles/PMC5129959/ /pubmed/27172797 http://dx.doi.org/10.18632/oncotarget.9243 Text en Copyright: © 2016 Bachmayr-Heyda 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
Bachmayr-Heyda, Anna
Auer, Katharina
Sukhbaatar, Nyamdelger
Aust, Stefanie
Deycmar, Simon
Reiner, Agnes T.
Polterauer, Stephan
Dekan, Sabine
Pils, Dietmar
Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread
title Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread
title_full Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread
title_fullStr Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread
title_full_unstemmed Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread
title_short Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread
title_sort small rnas and the competing endogenous rna network in high grade serous ovarian cancer tumor spread
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129959/
https://www.ncbi.nlm.nih.gov/pubmed/27172797
http://dx.doi.org/10.18632/oncotarget.9243
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