Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study
Abstract Background MicroRNAs (miRNAs) are promising biomarkers due to their structural stability and distinct expression profile in various cancers. We wanted to explore the miRNA expression in benign breast tissue and breast cancer subgroups in the Norwegian Women and Cancer study. Methods Specime...
Published in: | Journal of Translational Medicine |
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2019
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Online Access: | http://dx.doi.org/10.1186/s12967-019-2086-x http://link.springer.com/content/pdf/10.1186/s12967-019-2086-x.pdf http://link.springer.com/article/10.1186/s12967-019-2086-x/fulltext.html |
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crspringernat:10.1186/s12967-019-2086-x 2023-05-15T17:43:42+02:00 Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study Moi, Line Braaten, Tonje Al-Shibli, Khalid Lund, Eiliv Busund, Lill-Tove Rasmussen Helse Nord RHF 2019 http://dx.doi.org/10.1186/s12967-019-2086-x http://link.springer.com/content/pdf/10.1186/s12967-019-2086-x.pdf http://link.springer.com/article/10.1186/s12967-019-2086-x/fulltext.html en eng Springer Science and Business Media LLC http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ CC-BY Journal of Translational Medicine volume 17, issue 1 ISSN 1479-5876 General Biochemistry, Genetics and Molecular Biology General Medicine journal-article 2019 crspringernat https://doi.org/10.1186/s12967-019-2086-x 2022-01-04T07:58:26Z Abstract Background MicroRNAs (miRNAs) are promising biomarkers due to their structural stability and distinct expression profile in various cancers. We wanted to explore the miRNA expression in benign breast tissue and breast cancer subgroups in the Norwegian Women and Cancer study. Methods Specimens and histopathological data from study participants in Northern Norway diagnosed with breast cancer, and benign tissue from breast reduction surgery were collected. Main molecular subtypes were based on surrogate markers; luminal A (ER+ and/or PR+, HER2− and Ki67 ≤ 30%), luminal B (ER+ and/or PR+, HER2− and Ki67 > 30% or ER+ and/or PR+ and HER2+), HER2 positive (ER− and PR− and HER2+) and triple-negative (ER−, PR− and HER2−). RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue, and miRNAs were successfully analyzed in 102 cancers and 36 benign controls using the 7th generation miRCURY LNA microarray containing probes targeting all human miRNAs as annotated in miRBASE version 19.0. Validation with RT-qPCR was performed. Results On average, 450 miRNAs were detected in each sample, and 304 miRNAs were significantly different between malignant and benign tissue. Subgroup analyses of cancer cases revealed 23 miRNAs significantly different between ER+ and ER− tumors, and 47 miRNAs different between tumors stratified according to grade. Significantly higher levels were found in high grade tumors for miR-17-5p (p = 0.006), miR-20a-5p (p = 0.007), miR-106b-5p (p = 0.007), miR-93-5p (p = 0.007) and miR-25-3p (p = 0.015) from the paralogous clusters miR-17-92 and miR-106b-25. Expression of miR-17-5p (p = 0.0029), miR-20a-5p (p = 0.0021), miR-92a-3p (p = 0.011) and miR-106b-5p (p = 0.021) was significantly higher in triple-negative tumors compared to the rest, and miR-17-5p and miR-20a-5p were significantly lower in luminal A tumors. Conclusions miRNA expression profiles were significantly different between malignant and benign tissue and between cancer subgroups according to ER− status, grade and molecular subtype. miRNAs in the miR-17-92 cluster and miR-17 family were overexpressed in high grade and triple-negative tumors associated with aggressive behavior. The expression and functional role of these miRNAs should be further studied in breast cancer to explore their potential as biomarkers in diagnostic pathology and clinical oncology. Article in Journal/Newspaper Northern Norway Springer Nature (via Crossref) Norway Journal of Translational Medicine 17 1 |
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Springer Nature (via Crossref) |
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English |
topic |
General Biochemistry, Genetics and Molecular Biology General Medicine |
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General Biochemistry, Genetics and Molecular Biology General Medicine Moi, Line Braaten, Tonje Al-Shibli, Khalid Lund, Eiliv Busund, Lill-Tove Rasmussen Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study |
topic_facet |
General Biochemistry, Genetics and Molecular Biology General Medicine |
description |
Abstract Background MicroRNAs (miRNAs) are promising biomarkers due to their structural stability and distinct expression profile in various cancers. We wanted to explore the miRNA expression in benign breast tissue and breast cancer subgroups in the Norwegian Women and Cancer study. Methods Specimens and histopathological data from study participants in Northern Norway diagnosed with breast cancer, and benign tissue from breast reduction surgery were collected. Main molecular subtypes were based on surrogate markers; luminal A (ER+ and/or PR+, HER2− and Ki67 ≤ 30%), luminal B (ER+ and/or PR+, HER2− and Ki67 > 30% or ER+ and/or PR+ and HER2+), HER2 positive (ER− and PR− and HER2+) and triple-negative (ER−, PR− and HER2−). RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue, and miRNAs were successfully analyzed in 102 cancers and 36 benign controls using the 7th generation miRCURY LNA microarray containing probes targeting all human miRNAs as annotated in miRBASE version 19.0. Validation with RT-qPCR was performed. Results On average, 450 miRNAs were detected in each sample, and 304 miRNAs were significantly different between malignant and benign tissue. Subgroup analyses of cancer cases revealed 23 miRNAs significantly different between ER+ and ER− tumors, and 47 miRNAs different between tumors stratified according to grade. Significantly higher levels were found in high grade tumors for miR-17-5p (p = 0.006), miR-20a-5p (p = 0.007), miR-106b-5p (p = 0.007), miR-93-5p (p = 0.007) and miR-25-3p (p = 0.015) from the paralogous clusters miR-17-92 and miR-106b-25. Expression of miR-17-5p (p = 0.0029), miR-20a-5p (p = 0.0021), miR-92a-3p (p = 0.011) and miR-106b-5p (p = 0.021) was significantly higher in triple-negative tumors compared to the rest, and miR-17-5p and miR-20a-5p were significantly lower in luminal A tumors. Conclusions miRNA expression profiles were significantly different between malignant and benign tissue and between cancer subgroups according to ER− status, grade and molecular subtype. miRNAs in the miR-17-92 cluster and miR-17 family were overexpressed in high grade and triple-negative tumors associated with aggressive behavior. The expression and functional role of these miRNAs should be further studied in breast cancer to explore their potential as biomarkers in diagnostic pathology and clinical oncology. |
author2 |
Helse Nord RHF |
format |
Article in Journal/Newspaper |
author |
Moi, Line Braaten, Tonje Al-Shibli, Khalid Lund, Eiliv Busund, Lill-Tove Rasmussen |
author_facet |
Moi, Line Braaten, Tonje Al-Shibli, Khalid Lund, Eiliv Busund, Lill-Tove Rasmussen |
author_sort |
Moi, Line |
title |
Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study |
title_short |
Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study |
title_full |
Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study |
title_fullStr |
Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study |
title_full_unstemmed |
Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study |
title_sort |
differential expression of the mir-17-92 cluster and mir-17 family in breast cancer according to tumor type; results from the norwegian women and cancer (nowac) study |
publisher |
Springer Science and Business Media LLC |
publishDate |
2019 |
url |
http://dx.doi.org/10.1186/s12967-019-2086-x http://link.springer.com/content/pdf/10.1186/s12967-019-2086-x.pdf http://link.springer.com/article/10.1186/s12967-019-2086-x/fulltext.html |
geographic |
Norway |
geographic_facet |
Norway |
genre |
Northern Norway |
genre_facet |
Northern Norway |
op_source |
Journal of Translational Medicine volume 17, issue 1 ISSN 1479-5876 |
op_rights |
http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1186/s12967-019-2086-x |
container_title |
Journal of Translational Medicine |
container_volume |
17 |
container_issue |
1 |
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1766145849229836288 |