The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients
Bortezomib is the first-in-class proteasome inhibitor, commonly used in the treatment of multiple myeloma (MM). The mechanisms underlying acquired bortezomib resistance in MM are poorly understood. Several cell-free miRNAs have been found to be aberrantly regulated in MM patients. The aim of this pi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/9/2569 |
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| author | Paweł Robak Izabela Dróżdż Dariusz Jarych Damian Mikulski Edyta Węgłowska Monika Siemieniuk-Ryś Małgorzata Misiewicz Konrad Stawiski Wojciech Fendler Janusz Szemraj Piotr Smolewski Tadeusz Robak |
| author_facet | Paweł Robak Izabela Dróżdż Dariusz Jarych Damian Mikulski Edyta Węgłowska Monika Siemieniuk-Ryś Małgorzata Misiewicz Konrad Stawiski Wojciech Fendler Janusz Szemraj Piotr Smolewski Tadeusz Robak |
| author_sort | Paweł Robak |
| collection | DOAJ |
| description | Bortezomib is the first-in-class proteasome inhibitor, commonly used in the treatment of multiple myeloma (MM). The mechanisms underlying acquired bortezomib resistance in MM are poorly understood. Several cell-free miRNAs have been found to be aberrantly regulated in MM patients. The aim of this pilot study was to identify a blood-based miRNA signature that predicts bortezomib-based therapy efficacy in MM patients. Thirty MM patients treated with bortezomib-based regimens were studied, including 19 with refractory disease and 11 who were bortezomib sensitive. Serum miRNA expression patterns were identified with miRCURY LNA miRNA miRNome PCR Panels I+II (Exiqon/Qiagen). Univariate analysis found a total of 21 miRNAs to be differentially expressed in patients with MM according to bortezomib sensitivity. Multivariate logistic regression was created and allowed us to discriminate refractory from sensitive patients with a very high AUC of 0.95 (95%CI: 0.84–1.00); sensitivity, specificity and accuracy were estimated as 0.95, 0.91, and 0.93. The model used expression of 3 miRNAs: miR-215-5p, miR-181a-5p and miR-376c-3p. This study is the first to demonstrate that serum expression of several miRNAs differs between patients who are bortezomib refractory and those who are sensitive which may prove useful in studies aimed at overcoming drug resistance in MM treatment. |
| first_indexed | 2024-03-10T16:27:02Z |
| format | Article |
| id | doaj.art-08c18fb349014578b994456b9dc2c138 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T16:27:02Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-08c18fb349014578b994456b9dc2c1382023-11-20T13:06:34ZengMDPI AGCancers2072-66942020-09-01129256910.3390/cancers12092569The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma PatientsPaweł Robak0Izabela Dróżdż1Dariusz Jarych2Damian Mikulski3Edyta Węgłowska4Monika Siemieniuk-Ryś5Małgorzata Misiewicz6Konrad Stawiski7Wojciech Fendler8Janusz Szemraj9Piotr Smolewski10Tadeusz Robak11Department of Experimental Hematology, Medical University of Lodz, 93-510 Lodz, PolandDepartment of Clinical Genetics, Medical University of Lodz, 92-213 Lodz, PolandLaboratory of Personalized Medicine, Bionanopark, Lodz, 93-465 Lodz, PolandDepartment of Biostatistics and Translational Medicine, Medical University of Lodz, 92-215 Lodz, PolandLaboratory of Personalized Medicine, Bionanopark, Lodz, 93-465 Lodz, PolandDepartment of Hematology, Medical University of Lodz, 93-510 Lodz, PolandDepartment of Hematology, Medical University of Lodz, 93-510 Lodz, PolandDepartment of Biostatistics and Translational Medicine, Medical University of Lodz, 92-215 Lodz, PolandDepartment of Biostatistics and Translational Medicine, Medical University of Lodz, 92-215 Lodz, PolandDepartment of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, PolandDepartment of Experimental Hematology, Medical University of Lodz, 93-510 Lodz, PolandDepartment of Hematology, Medical University of Lodz, 93-510 Lodz, PolandBortezomib is the first-in-class proteasome inhibitor, commonly used in the treatment of multiple myeloma (MM). The mechanisms underlying acquired bortezomib resistance in MM are poorly understood. Several cell-free miRNAs have been found to be aberrantly regulated in MM patients. The aim of this pilot study was to identify a blood-based miRNA signature that predicts bortezomib-based therapy efficacy in MM patients. Thirty MM patients treated with bortezomib-based regimens were studied, including 19 with refractory disease and 11 who were bortezomib sensitive. Serum miRNA expression patterns were identified with miRCURY LNA miRNA miRNome PCR Panels I+II (Exiqon/Qiagen). Univariate analysis found a total of 21 miRNAs to be differentially expressed in patients with MM according to bortezomib sensitivity. Multivariate logistic regression was created and allowed us to discriminate refractory from sensitive patients with a very high AUC of 0.95 (95%CI: 0.84–1.00); sensitivity, specificity and accuracy were estimated as 0.95, 0.91, and 0.93. The model used expression of 3 miRNAs: miR-215-5p, miR-181a-5p and miR-376c-3p. This study is the first to demonstrate that serum expression of several miRNAs differs between patients who are bortezomib refractory and those who are sensitive which may prove useful in studies aimed at overcoming drug resistance in MM treatment.https://www.mdpi.com/2072-6694/12/9/2569bortezomibefficacymultiple myelomaresistancesensitivityrefractory |
| spellingShingle | Paweł Robak Izabela Dróżdż Dariusz Jarych Damian Mikulski Edyta Węgłowska Monika Siemieniuk-Ryś Małgorzata Misiewicz Konrad Stawiski Wojciech Fendler Janusz Szemraj Piotr Smolewski Tadeusz Robak The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients Cancers bortezomib efficacy multiple myeloma resistance sensitivity refractory |
| title | The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients |
| title_full | The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients |
| title_fullStr | The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients |
| title_full_unstemmed | The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients |
| title_short | The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients |
| title_sort | value of serum microrna expression signature in predicting refractoriness to bortezomib based therapy in multiple myeloma patients |
| topic | bortezomib efficacy multiple myeloma resistance sensitivity refractory |
| url | https://www.mdpi.com/2072-6694/12/9/2569 |
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