Plasma microRNA ratios associated with breast cancer detection in a nested case–control study from a mammography screening cohort
Abstract Mammographic breast cancer screening is effective in reducing breast cancer mortality. Nevertheless, several limitations are known. Therefore, developing an alternative or complementary non-invasive tool capable of increasing the accuracy of the screening process is highly desirable. The ob...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38886-0 |
| _version_ | 1827890430501453824 |
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| author | Giovanna Chiorino Elisabetta Petracci Emir Sehovic Ilaria Gregnanin Elisa Camussi Maurizia Mello-Grand Paola Ostano Emilia Riggi Viviana Vergini Alessia Russo Enrico Berrino Andrea Ortale Francesca Garena Tiziana Venesio Federica Gallo Elisabetta Favettini Alfonso Frigerio Giuseppe Matullo Nereo Segnan Livia Giordano |
| author_facet | Giovanna Chiorino Elisabetta Petracci Emir Sehovic Ilaria Gregnanin Elisa Camussi Maurizia Mello-Grand Paola Ostano Emilia Riggi Viviana Vergini Alessia Russo Enrico Berrino Andrea Ortale Francesca Garena Tiziana Venesio Federica Gallo Elisabetta Favettini Alfonso Frigerio Giuseppe Matullo Nereo Segnan Livia Giordano |
| author_sort | Giovanna Chiorino |
| collection | DOAJ |
| description | Abstract Mammographic breast cancer screening is effective in reducing breast cancer mortality. Nevertheless, several limitations are known. Therefore, developing an alternative or complementary non-invasive tool capable of increasing the accuracy of the screening process is highly desirable. The objective of this study was to identify circulating microRNA (miRs) ratios associated with BC in women attending mammography screening. A nested case–control study was conducted within the ANDROMEDA cohort (women of age 46–67 attending BC screening). Pre-diagnostic plasma samples, information on life-styles and common BC risk factors were collected. Small-RNA sequencing was carried out on plasma samples from 65 cases and 66 controls. miR ratios associated with BC were selected by two-sample Wilcoxon test and lasso logistic regression. Subsequent assessment by RT-qPCR of the miRs contained in the selected miR ratios was carried out as a platform validation. To identify the most promising biomarkers, penalised logistic regression was further applied to candidate miR ratios alone, or in combination with non-molecular factors. Small-RNA sequencing yielded 20 candidate miR ratios associated with BC, which were further assessed by RT-qPCR. In the resulting model, penalised logistic regression selected seven miR ratios (miR-199a-3p_let-7a-5p, miR-26b-5p_miR-142-5p, let-7b-5p_miR-19b-3p, miR-101-3p_miR-19b-3p, miR-93-5p_miR-19b-3p, let-7a-5p_miR-22-3p and miR-21-5p_miR-23a-3p), together with body mass index (BMI), menopausal status (MS), the interaction term BMI * MS, life-style score and breast density. The ROC AUC of the model was 0.79 with a sensitivity and specificity of 71.9% and 76.6%, respectively. We identified biomarkers potentially useful for BC screening measured through a widespread and low-cost technique. This is the first study reporting circulating miRs for BC detection in a screening setting. Validation in a wider sample is warranted. Trial registration: The Andromeda prospective cohort study protocol was retrospectively registered on 27-11-2015 (NCT02618538). |
| first_indexed | 2024-03-12T21:09:37Z |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T21:09:37Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-044deb74a3a04e07afe4fafc799eea7d2023-07-30T11:15:06ZengNature PortfolioScientific Reports2045-23222023-07-0113111410.1038/s41598-023-38886-0Plasma microRNA ratios associated with breast cancer detection in a nested case–control study from a mammography screening cohortGiovanna Chiorino0Elisabetta Petracci1Emir Sehovic2Ilaria Gregnanin3Elisa Camussi4Maurizia Mello-Grand5Paola Ostano6Emilia Riggi7Viviana Vergini8Alessia Russo9Enrico Berrino10Andrea Ortale11Francesca Garena12Tiziana Venesio13Federica Gallo14Elisabetta Favettini15Alfonso Frigerio16Giuseppe Matullo17Nereo Segnan18Livia Giordano19Cancer Genomics Lab, Fondazione Edo ed Elvo TempiaUnit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”Cancer Genomics Lab, Fondazione Edo ed Elvo TempiaCancer Genomics Lab, Fondazione Edo ed Elvo TempiaSSD Epidemiologia Screening, CPO-AOU Città della Salute e della Scienza di TorinoCancer Genomics Lab, Fondazione Edo ed Elvo TempiaCancer Genomics Lab, Fondazione Edo ed Elvo TempiaSSD Epidemiologia Screening, CPO-AOU Città della Salute e della Scienza di TorinoSSD Epidemiologia Screening, CPO-AOU Città della Salute e della Scienza di TorinoDepartment of Medical Sciences, University of TurinDepartment of Medical Sciences, University of TurinSSD Epidemiologia Screening, CPO-AOU Città della Salute e della Scienza di TorinoSSD Epidemiologia Screening, CPO-AOU Città della Salute e della Scienza di TorinoPathology Unit, Candiolo Cancer Institute, FPO IRCCSEpidemiology Unit, Staff Health Direction, Local Health Authority 1 of CuneoDiagnostic Radiology Unit, Nuovo Ospedale Degli InfermiSSD Epidemiologia Screening, CPO-AOU Città della Salute e della Scienza di TorinoDepartment of Medical Sciences, University of TurinSSD Epidemiologia Screening, CPO-AOU Città della Salute e della Scienza di TorinoSSD Epidemiologia Screening, CPO-AOU Città della Salute e della Scienza di TorinoAbstract Mammographic breast cancer screening is effective in reducing breast cancer mortality. Nevertheless, several limitations are known. Therefore, developing an alternative or complementary non-invasive tool capable of increasing the accuracy of the screening process is highly desirable. The objective of this study was to identify circulating microRNA (miRs) ratios associated with BC in women attending mammography screening. A nested case–control study was conducted within the ANDROMEDA cohort (women of age 46–67 attending BC screening). Pre-diagnostic plasma samples, information on life-styles and common BC risk factors were collected. Small-RNA sequencing was carried out on plasma samples from 65 cases and 66 controls. miR ratios associated with BC were selected by two-sample Wilcoxon test and lasso logistic regression. Subsequent assessment by RT-qPCR of the miRs contained in the selected miR ratios was carried out as a platform validation. To identify the most promising biomarkers, penalised logistic regression was further applied to candidate miR ratios alone, or in combination with non-molecular factors. Small-RNA sequencing yielded 20 candidate miR ratios associated with BC, which were further assessed by RT-qPCR. In the resulting model, penalised logistic regression selected seven miR ratios (miR-199a-3p_let-7a-5p, miR-26b-5p_miR-142-5p, let-7b-5p_miR-19b-3p, miR-101-3p_miR-19b-3p, miR-93-5p_miR-19b-3p, let-7a-5p_miR-22-3p and miR-21-5p_miR-23a-3p), together with body mass index (BMI), menopausal status (MS), the interaction term BMI * MS, life-style score and breast density. The ROC AUC of the model was 0.79 with a sensitivity and specificity of 71.9% and 76.6%, respectively. We identified biomarkers potentially useful for BC screening measured through a widespread and low-cost technique. This is the first study reporting circulating miRs for BC detection in a screening setting. Validation in a wider sample is warranted. Trial registration: The Andromeda prospective cohort study protocol was retrospectively registered on 27-11-2015 (NCT02618538).https://doi.org/10.1038/s41598-023-38886-0 |
| spellingShingle | Giovanna Chiorino Elisabetta Petracci Emir Sehovic Ilaria Gregnanin Elisa Camussi Maurizia Mello-Grand Paola Ostano Emilia Riggi Viviana Vergini Alessia Russo Enrico Berrino Andrea Ortale Francesca Garena Tiziana Venesio Federica Gallo Elisabetta Favettini Alfonso Frigerio Giuseppe Matullo Nereo Segnan Livia Giordano Plasma microRNA ratios associated with breast cancer detection in a nested case–control study from a mammography screening cohort Scientific Reports |
| title | Plasma microRNA ratios associated with breast cancer detection in a nested case–control study from a mammography screening cohort |
| title_full | Plasma microRNA ratios associated with breast cancer detection in a nested case–control study from a mammography screening cohort |
| title_fullStr | Plasma microRNA ratios associated with breast cancer detection in a nested case–control study from a mammography screening cohort |
| title_full_unstemmed | Plasma microRNA ratios associated with breast cancer detection in a nested case–control study from a mammography screening cohort |
| title_short | Plasma microRNA ratios associated with breast cancer detection in a nested case–control study from a mammography screening cohort |
| title_sort | plasma microrna ratios associated with breast cancer detection in a nested case control study from a mammography screening cohort |
| url | https://doi.org/10.1038/s41598-023-38886-0 |
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