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Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer
BACKGROUND: There is a critical need for improved diagnostic markers for high grade serous epithelial ovarian cancer (SEOC). MicroRNAs are stable in the circulation and may have utility as biomarkers of malignancy. We investigated whether levels of serum microRNA could discriminate women with high-g...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542279/ https://www.ncbi.nlm.nih.gov/pubmed/23272653 http://dx.doi.org/10.1186/1471-2407-12-627 |
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author | Kan, Casina WS Hahn, Michael A Gard, Gregory B Maidens, Jayne Huh, Jung Yoon Marsh, Deborah J Howell, Viive M |
author_facet | Kan, Casina WS Hahn, Michael A Gard, Gregory B Maidens, Jayne Huh, Jung Yoon Marsh, Deborah J Howell, Viive M |
author_sort | Kan, Casina WS |
collection | PubMed |
description | BACKGROUND: There is a critical need for improved diagnostic markers for high grade serous epithelial ovarian cancer (SEOC). MicroRNAs are stable in the circulation and may have utility as biomarkers of malignancy. We investigated whether levels of serum microRNA could discriminate women with high-grade SEOC from age matched healthy volunteers. METHODS: To identify microRNA of interest, microRNA expression profiling was performed on 4 SEOC cell lines and normal human ovarian surface epithelial cells. Total RNA was extracted from 500 μL aliquots of serum collected from patients with SEOC (n = 28) and age-matched healthy donors (n = 28). Serum microRNA levels were assessed by quantitative RT-PCR following preamplification. RESULTS: microRNA (miR)-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers. miR-103, miR-92a and miR -638 had relatively invariant expression across all ovarian cell lines, and with small-nucleolar C/D box 48 (RNU48) were assessed in RNA extracted from serum as candidate endogenous normalizers. No correlation between serum levels and age were observed (age range 30-79 years) for any of these microRNA or RNU48. Individually, miR-200a, miR-200b and miR-200c normalized to serum volume and miR-103 were significantly higher in serum of the SEOC cohort (P < 0.05; 0.05; 0.0005 respectively) and in combination, miR-200b + miR-200c normalized to serum volume and miR-103 was the best predictive classifier of SEOC (ROC-AUC = 0.784). This predictive model (miR-200b + miR-200c) was further confirmed by leave one out cross validation (AUC = 0.784). CONCLUSIONS: We identified serum microRNAs able to discriminate patients with high grade SEOC from age-matched healthy controls. The addition of these microRNAs to current testing regimes may improve diagnosis for women with SEOC. |
format | Online Article Text |
id | pubmed-3542279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35422792013-01-11 Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer Kan, Casina WS Hahn, Michael A Gard, Gregory B Maidens, Jayne Huh, Jung Yoon Marsh, Deborah J Howell, Viive M BMC Cancer Research Article BACKGROUND: There is a critical need for improved diagnostic markers for high grade serous epithelial ovarian cancer (SEOC). MicroRNAs are stable in the circulation and may have utility as biomarkers of malignancy. We investigated whether levels of serum microRNA could discriminate women with high-grade SEOC from age matched healthy volunteers. METHODS: To identify microRNA of interest, microRNA expression profiling was performed on 4 SEOC cell lines and normal human ovarian surface epithelial cells. Total RNA was extracted from 500 μL aliquots of serum collected from patients with SEOC (n = 28) and age-matched healthy donors (n = 28). Serum microRNA levels were assessed by quantitative RT-PCR following preamplification. RESULTS: microRNA (miR)-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers. miR-103, miR-92a and miR -638 had relatively invariant expression across all ovarian cell lines, and with small-nucleolar C/D box 48 (RNU48) were assessed in RNA extracted from serum as candidate endogenous normalizers. No correlation between serum levels and age were observed (age range 30-79 years) for any of these microRNA or RNU48. Individually, miR-200a, miR-200b and miR-200c normalized to serum volume and miR-103 were significantly higher in serum of the SEOC cohort (P < 0.05; 0.05; 0.0005 respectively) and in combination, miR-200b + miR-200c normalized to serum volume and miR-103 was the best predictive classifier of SEOC (ROC-AUC = 0.784). This predictive model (miR-200b + miR-200c) was further confirmed by leave one out cross validation (AUC = 0.784). CONCLUSIONS: We identified serum microRNAs able to discriminate patients with high grade SEOC from age-matched healthy controls. The addition of these microRNAs to current testing regimes may improve diagnosis for women with SEOC. BioMed Central 2012-12-28 /pmc/articles/PMC3542279/ /pubmed/23272653 http://dx.doi.org/10.1186/1471-2407-12-627 Text en Copyright ©2012 Kan et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Kan, Casina WS Hahn, Michael A Gard, Gregory B Maidens, Jayne Huh, Jung Yoon Marsh, Deborah J Howell, Viive M Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer |
title | Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer |
title_full | Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer |
title_fullStr | Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer |
title_full_unstemmed | Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer |
title_short | Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer |
title_sort | elevated levels of circulating microrna-200 family members correlate with serous epithelial ovarian cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542279/ https://www.ncbi.nlm.nih.gov/pubmed/23272653 http://dx.doi.org/10.1186/1471-2407-12-627 |
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