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Di Cosimo, Serena; Appierto, Valentina; Pizzamiglio, Sara; Silvestri, Marco; Baselga, José; Piccart, Martine; Huober, Jens; Izquierdo, Miguel; de la Pena, Lorena; Hilbers, Florentine S; de Azambuja, Evandro; Untch, Michael; Pusztai, Lajos; Pritchard, Kathleen; Nuciforo, Paolo; Vincent-Salomon, Anne; Symmans, Fraser; Apolone, Giovanni; de Braud, Filippo G; Iorio, Marilena V; Verderio, Paolo; Daidone, Maria Grazia
International journal of molecular sciences, 02/2020, Volume: 21, Issue: 4Journal Article
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) ( = 0.008 and 0.048, respectively). At a threshold ≥ the upper limit of the 95%CI of the mean difference, pCR resulted 45% (95%CI 24%-68%), and 44% (95%CI 22%-69%) for ct-miR-148a-3p and ct-miR-374a-5p, respectively. Notably, ct-miR-148a-3p retained its predictive value (OR 3.42, 95%CI 1.23-9.46, = 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 54% (95%CI 25%-81%) and 0% (95%CI 0%-31%) 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.
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