TY  - JOUR
A1  - Curtaz, Carolin J.
A1  - Reifschläger, Leonie
A1  - Strähle, Linus
A1  - Feldheim, Jonas
A1  - Feldheim, Julia J.
A1  - Schmitt, Constanze
A1  - Kiesel, Matthias
A1  - Herbert, Saskia-Laureen
A1  - Wöckel, Achim
A1  - Meybohm, Patrick
A1  - Burek, Malgorzata
T1  - Analysis of microRNAs in exosomes of breast cancer patients in search of molecular prognostic factors in brain metastases
T2  - International Journal of Molecular Sciences
N2  - 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.
KW  - breast cancer
KW  - breast cancer metastases
KW  - blood-brain barrier
KW  - patient serum
KW  - exosomes
KW  - microRNA
KW  - gene expression
KW  - prognostic marker
Y1  - 2022
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/28447
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-284476
SN  - 1422-0067
VL  - 23
IS  - 7
ER  -