Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases
Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/7/3683 |
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| author | Carolin J. Curtaz Leonie Reifschläger Linus Strähle Jonas Feldheim Julia J. Feldheim Constanze Schmitt Matthias Kiesel Saskia-Laureen Herbert Achim Wöckel Patrick Meybohm Malgorzata Burek |
| author_facet | Carolin J. Curtaz Leonie Reifschläger Linus Strähle Jonas Feldheim Julia J. Feldheim Constanze Schmitt Matthias Kiesel Saskia-Laureen Herbert Achim Wöckel Patrick Meybohm Malgorzata Burek |
| author_sort | Carolin J. Curtaz |
| collection | DOAJ |
| description | Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use. |
| first_indexed | 2024-03-09T11:46:58Z |
| format | Article |
| id | doaj.art-eb129504929c48f589fe776df757f2c2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:46:58Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-eb129504929c48f589fe776df757f2c22023-11-30T23:20:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237368310.3390/ijms23073683Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain MetastasesCarolin J. Curtaz0Leonie Reifschläger1Linus Strähle2Jonas Feldheim3Julia J. Feldheim4Constanze Schmitt5Matthias Kiesel6Saskia-Laureen Herbert7Achim Wöckel8Patrick Meybohm9Malgorzata Burek10Department of Gynecology and Obsterics, University Hospital Würzburg, 97080 Würzburg, GermanyDepartment of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, 97080 Würzburg, GermanyDepartment of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, 97080 Würzburg, GermanyCenter for Translational Neuro- and Behavioral Sciences, University Hospital Essen, 45147 Essen, GermanyDepartment of Neurosurgery, University Hospital Essen, 45147 Essen, GermanyDepartment of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, 97080 Würzburg, GermanyDepartment of Gynecology and Obsterics, University Hospital Würzburg, 97080 Würzburg, GermanyDepartment of Gynecology and Obsterics, University Hospital Würzburg, 97080 Würzburg, GermanyDepartment of Gynecology and Obsterics, University Hospital Würzburg, 97080 Würzburg, GermanyDepartment of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, 97080 Würzburg, GermanyDepartment of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, 97080 Würzburg, GermanyBrain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.https://www.mdpi.com/1422-0067/23/7/3683breast cancerbreast cancer metastasesblood-brain barrierpatient serumexosomesmicroRNA |
| spellingShingle | Carolin J. Curtaz Leonie Reifschläger Linus Strähle Jonas Feldheim Julia J. Feldheim Constanze Schmitt Matthias Kiesel Saskia-Laureen Herbert Achim Wöckel Patrick Meybohm Malgorzata Burek Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases International Journal of Molecular Sciences breast cancer breast cancer metastases blood-brain barrier patient serum exosomes microRNA |
| title | Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases |
| title_full | Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases |
| title_fullStr | Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases |
| title_full_unstemmed | Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases |
| title_short | Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases |
| title_sort | analysis of micrornas in exosomes of breast cancer patients in search of molecular prognostic factors in brain metastases |
| topic | breast cancer breast cancer metastases blood-brain barrier patient serum exosomes microRNA |
| url | https://www.mdpi.com/1422-0067/23/7/3683 |
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