TY - JOUR
T1 - Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy.
AU - Di Cosimo, Serena
AU - Appierto, Valentina
AU - Pizzamiglio, Sara
AU - Silvestri, Marco
AU - Baselga, José
AU - Piccart, Martine
AU - Huober, Jens
AU - Izquierdo, Miguel
AU - de la Pena, Lorena
AU - Hilbers, Florentine S.
AU - de Azambuja, Evandro
AU - Untch, Michael
AU - Pusztai, Lajos
AU - Pritchard, Kathleen
AU - Nuciforo, Paolo
AU - Vincent-Salomon, Anne
AU - Symmans, Fraser
AU - Apolone, Giovanni
AU - de Braud, Filippo G.
AU - Iorio, Marilena V.
AU - Verderio, Paolo
AU - Daidone, Maria Grazia
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3p and ct-miR-374a-5p were significantly associated with pathological complete response (pCR) (p = 0.008 and 0.048, respectively). At a threshold ≥ the upper limit of the 95 pCR resulted 4595468, and 4495269 for ct-miR-148a-3p and ct-miR-374a-5p, respectively. Notably, ct-miR-148a-3p retained its predictive value (OR 3.42, 95.23-9.46, p = 0.018) in bivariate analysis along with estrogen receptor status. Combined information from ct-miR-148a-3p and ct-miR140-5p, which we previously reported to identify trastuzumab-responsive patients, resulted in greater predictive capability over each other, with pCR of 5495581 and 09531 in ct-miR-148a/ct-miR-140-5p high/present and low/absent, respectively. GO and KEGG analyses showed common enriched terms between the targets of these ct-miRNAs, including cell metabolism regulation, AMPK and MAPK signaling, and HCC progression. In conclusion, early modulated ct-miR-148-3p may inform on the functional processes underlying treatment response, integrate the information from already available predictive biomarkers, and identify patients likely to respond to single agent trastuzumab-based neoadjuvant therapy.
AB - Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3p and ct-miR-374a-5p were significantly associated with pathological complete response (pCR) (p = 0.008 and 0.048, respectively). At a threshold ≥ the upper limit of the 95 pCR resulted 4595468, and 4495269 for ct-miR-148a-3p and ct-miR-374a-5p, respectively. Notably, ct-miR-148a-3p retained its predictive value (OR 3.42, 95.23-9.46, p = 0.018) in bivariate analysis along with estrogen receptor status. Combined information from ct-miR-148a-3p and ct-miR140-5p, which we previously reported to identify trastuzumab-responsive patients, resulted in greater predictive capability over each other, with pCR of 5495581 and 09531 in ct-miR-148a/ct-miR-140-5p high/present and low/absent, respectively. GO and KEGG analyses showed common enriched terms between the targets of these ct-miRNAs, including cell metabolism regulation, AMPK and MAPK signaling, and HCC progression. In conclusion, early modulated ct-miR-148-3p may inform on the functional processes underlying treatment response, integrate the information from already available predictive biomarkers, and identify patients likely to respond to single agent trastuzumab-based neoadjuvant therapy.
KW - Adult
KW - Female
KW - Humans
KW - Middle Aged
KW - Multivariate Analysis
KW - breast cancer
KW - trastuzumab
KW - biomarkers
KW - Aged
KW - Logistic Models
KW - Cell Line
KW - Tumor
KW - HER2
KW - circulating microRNAs
KW - ct-miR-148a-3p
KW - Gene Regulatory Networks
KW - Neoadjuvant Therapy
KW - Receptor
KW - ErbB-2/metabolism
KW - Breast Neoplasms/blood/drug therapy/genetics
KW - Circulating MicroRNA/blood
KW - Gene Expression Regulation
KW - Neoplastic
KW - Trastuzumab/therapeutic use
U2 - 10.3390/ijms21041386
DO - 10.3390/ijms21041386
M3 - Article
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 4
ER -