Elevated miR-29c-5p Expression in Nipple Aspirate Fluid Is Associated with Extremely High Mammographic Breast Density
High mammographic density (MD) is associated with an increased risk of breast cancer, however the underlying mechanisms are largely unknown. This research aimed to identify microRNAs (miRNAs) that play a role in the development of extremely dense breast tissue. In the discovery phase, 754 human matu...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/15/3805 |
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| author | Tessa A. C. M. Vissers Leonie Piek Susana I. S. Patuleia Aafke J. Duinmeijer Marije F. Bakker Elsken van der Wall Paul J. van Diest Carla H. van Gils Cathy B. Moelans |
| author_facet | Tessa A. C. M. Vissers Leonie Piek Susana I. S. Patuleia Aafke J. Duinmeijer Marije F. Bakker Elsken van der Wall Paul J. van Diest Carla H. van Gils Cathy B. Moelans |
| author_sort | Tessa A. C. M. Vissers |
| collection | DOAJ |
| description | High mammographic density (MD) is associated with an increased risk of breast cancer, however the underlying mechanisms are largely unknown. This research aimed to identify microRNAs (miRNAs) that play a role in the development of extremely dense breast tissue. In the discovery phase, 754 human mature miRNAs were profiled in 21 extremely high MD- and 20 very low MD-derived nipple aspirate fluid (NAF) samples from healthy women. In the validation phase, candidate miRNAs were assessed in a cohort of 89 extremely high MD and 81 very low MD NAF samples from healthy women. Independent predictors of either extremely high MD or miRNA expression were identified by logistic regression and linear regression analysis, respectively. mRNA targets and pathways were identified through miRTarBase, TargetScan, and PANTHER pathway analysis. Statistical analysis identified four differentially expressed miRNAs during the discovery phase. During the validation, linear regression (<i>p</i> = 0.029; fold change = 2.10) and logistic regression (<i>p</i> = 0.048; odds ratio = 1.38) showed that hsa-miR-29c-5p was upregulated in extremely high MD-derived NAF. Identified candidate mRNA targets of hsa-miR-29c-5p are CFLAR, DNMT3A, and PTEN. Further validation and exploration of targets and downstream pathways of has-miR-29c-5p will provide better insight into the processes involved in the development of high MD and in the associated increased risk of breast cancer. |
| first_indexed | 2024-03-09T12:44:24Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T12:44:24Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f506976757e3422783a331b1079c8d7b2023-11-30T22:15:01ZengMDPI AGCancers2072-66942022-08-011415380510.3390/cancers14153805Elevated miR-29c-5p Expression in Nipple Aspirate Fluid Is Associated with Extremely High Mammographic Breast DensityTessa A. C. M. Vissers0Leonie Piek1Susana I. S. Patuleia2Aafke J. Duinmeijer3Marije F. Bakker4Elsken van der Wall5Paul J. van Diest6Carla H. van Gils7Cathy B. Moelans8Department of Pathology, University Medical Center Utrecht, 3508 GA Utrecht, The NetherlandsDepartment of Pathology, University Medical Center Utrecht, 3508 GA Utrecht, The NetherlandsDepartment of Pathology, University Medical Center Utrecht, 3508 GA Utrecht, The NetherlandsDepartment of Medical Oncology, University Medical Center Utrecht, 3508 GA Utrecht, The NetherlandsDepartment of Epidemiology of the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3508 GA Utrecht, The NetherlandsDepartment of Medical Oncology, University Medical Center Utrecht, 3508 GA Utrecht, The NetherlandsDepartment of Pathology, University Medical Center Utrecht, 3508 GA Utrecht, The NetherlandsDepartment of Epidemiology of the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3508 GA Utrecht, The NetherlandsDepartment of Pathology, University Medical Center Utrecht, 3508 GA Utrecht, The NetherlandsHigh mammographic density (MD) is associated with an increased risk of breast cancer, however the underlying mechanisms are largely unknown. This research aimed to identify microRNAs (miRNAs) that play a role in the development of extremely dense breast tissue. In the discovery phase, 754 human mature miRNAs were profiled in 21 extremely high MD- and 20 very low MD-derived nipple aspirate fluid (NAF) samples from healthy women. In the validation phase, candidate miRNAs were assessed in a cohort of 89 extremely high MD and 81 very low MD NAF samples from healthy women. Independent predictors of either extremely high MD or miRNA expression were identified by logistic regression and linear regression analysis, respectively. mRNA targets and pathways were identified through miRTarBase, TargetScan, and PANTHER pathway analysis. Statistical analysis identified four differentially expressed miRNAs during the discovery phase. During the validation, linear regression (<i>p</i> = 0.029; fold change = 2.10) and logistic regression (<i>p</i> = 0.048; odds ratio = 1.38) showed that hsa-miR-29c-5p was upregulated in extremely high MD-derived NAF. Identified candidate mRNA targets of hsa-miR-29c-5p are CFLAR, DNMT3A, and PTEN. Further validation and exploration of targets and downstream pathways of has-miR-29c-5p will provide better insight into the processes involved in the development of high MD and in the associated increased risk of breast cancer.https://www.mdpi.com/2072-6694/14/15/3805miRNAmammographic densitybreast cancernipple aspirate fluid |
| spellingShingle | Tessa A. C. M. Vissers Leonie Piek Susana I. S. Patuleia Aafke J. Duinmeijer Marije F. Bakker Elsken van der Wall Paul J. van Diest Carla H. van Gils Cathy B. Moelans Elevated miR-29c-5p Expression in Nipple Aspirate Fluid Is Associated with Extremely High Mammographic Breast Density Cancers miRNA mammographic density breast cancer nipple aspirate fluid |
| title | Elevated miR-29c-5p Expression in Nipple Aspirate Fluid Is Associated with Extremely High Mammographic Breast Density |
| title_full | Elevated miR-29c-5p Expression in Nipple Aspirate Fluid Is Associated with Extremely High Mammographic Breast Density |
| title_fullStr | Elevated miR-29c-5p Expression in Nipple Aspirate Fluid Is Associated with Extremely High Mammographic Breast Density |
| title_full_unstemmed | Elevated miR-29c-5p Expression in Nipple Aspirate Fluid Is Associated with Extremely High Mammographic Breast Density |
| title_short | Elevated miR-29c-5p Expression in Nipple Aspirate Fluid Is Associated with Extremely High Mammographic Breast Density |
| title_sort | elevated mir 29c 5p expression in nipple aspirate fluid is associated with extremely high mammographic breast density |
| topic | miRNA mammographic density breast cancer nipple aspirate fluid |
| url | https://www.mdpi.com/2072-6694/14/15/3805 |
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