Liquid biopsies: a new emerging strategy for the early detection of breast cancer.

FARRÉ PL; DALTON GN; DUCA RB; PICCIONI F; MASSILLO C; SCALISE G; DIMASE F; BATAGELJ E; CASALNUOVO M; GALLAND M; FARIAS R; GUSCELLI C; DE SIERVI A

Mar del Plata, Buenos Aires, Argentina

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

SAIC

Breast cancer (BCa) is the leading cause of death by cancer in women worldwide. Even though early diagnosis is improving the survival of BCa patients, more sensitive and specific tools are still necessary. Here, we propose the use of miRNAs as a biomarker alternative in BCa diagnosis. miRNAs are small non-coding RNA molecules that can be found in body fluids, such as urine or blood. Additionally, miRNAs can be release by tumors in early stages of BCa, even when they are undetectable by other diagnostic methods, which makes these molecules useful tools for early BCa detection.The aim of this work was to identify circulating miRNAs (liquid biopsies) in plasma of BCa patients at different stages using microarrays and mice model validation. For this purpose, plasma from 30 BCa patients was distributed into 5 clusters, according with their BCa stage: i) stages 0 and IA, ii) stage IIA, iii) stage IIB, iv) stage IIIA, and v) stages IIIB, IIIC and IV. As control, plasma from 32 healthy donors was distributed into 4 clusters. We hybridized miRNAs of each group using GeneChip® miRNA 4.0 Array (Affymetrix). Data analysis showed that miR-93-5p, -150-5p, -3178, -4459, -4467, -4486, -4730, -6514-3p, -6716-3p, -7107-5p and -7110-5p were upregulated in the plasma from BCa patients compared to healthy donors.Analytical validation of these results was performed in NOD scid gamma (NSG) mice. We inoculated female mice with BCa cell line MDA-MB-231 (BCa mice). After tumor growth, we sacrificed the mice to collect blood and tumor samples. Plasma from healthy animals was also obtained (control mice). We tested all miRNAs obtained from microarrays analysis from patients. Xenografts expressed miR-93-5p, -150-5p, -3178, -4467 and -6716-3p, being miR-3178 the most expressed. We detected several circulating miRNAs in the plasma of these animals. Interestingly, miR-93-5p was found significantly enriched in the plasma from BCa mice compared to control mice.