MicroRNA-27a-5p (miR-27a-5p) has been closely related to the pathogenesis of different solid tumors, showing potentials as both useful biomarker and druggable target of clinical application. In our study, we performed the expression analysis of miR-27a-5p in a retrospective cohort of 232 breast cancer (BC) patients with a median follow-up of 99.4 months enrolled according to the REMARK guidelines. Of those patients, 9 showed synchronous metastases (MTX), 45 developed metastases during the follow-up time (M0>M1), and 178 were free from metastases after a follow-up of at least 5 years (M0). As controls, 13 normal breast tissues (NBTs) from reductive mammoplasty and 11 pre-invasive breast lesions (PreBr) were also profiled. Overall, miR-27a-5p showed higher levels in NBTs (Median 2.28, IQR 1.50-5.40) and pre-invasive breast lesions (Median 3.32, IQR 1.68-4.32) compared to tumour samples. In particular, miR-27a-5p was less expressed in patients with synchronous (Median 1.03 IQR 0.83-1.58) or metachronous (Median 1.83, IQR 1.29-3.17) metastases than in patients free from metastases after a 5-year follow-up (Median 2.17, IQR 1.19-3.64). Thus, we found that miR-27a-5p expression (log values) is negatively correlated with breast pathology evolution (R= -0.13, P=0.038). Next, we assessed the potentialities of miR-27a-5p as BC-specific prognostic biomarker in the subgroup of patients without metastases at diagnosis (n=222). Moreover, increased miR-27a-5p levels were associated with reduced risk of disease progression (Progression Free Survival (PFS) HR 0.43, 95%CI 0.18-0.99, P=0.048), metastases development (Metastases Free survival (MFS) HR 0.42, 95%CI 0.18-0.96, P=0.039), and cancer-related death (Overall Survival (OS) HR 0.30, 95%CI 0.12-0.74, P=0.009) in the subgroup of HER2-amplified tumours (n=26). Then, we extended our analysis to the TCGA BRCA dataset by selecting a total of 561 cases without synchronous metastases, for whom miR-27a-5p expression levels, and clinical and follow-up data were available. Among them, 19 were HER2 amplified according to clinical guidelines (i.e. score 3+ at immunostaining or FISH-positive). Similarly to our internal cohort, high miR-27a-5p was associated to reduced risk of disease progression (PFS HR 0.61, 95%CI 0.10-3.61) and death (OS HR 0.62, 95%CI 0.08-5.05) in the subgroup of HER2-amplified cases, although the association did not reach statistical significance. Overall, our data support the tumour suppressive role of miR-27a-5p in breast cancer, and suggest miR-27a-5p as putative prognostic biomarker in HER2-amplified tumours.

Citation Format: Barbara Pasculli, Andrea Fontana, Serena Barile, Morritti Maria, Luigi Ciuffreda, Paolo Graziano, Evaristo Maiello, Paola Parrella. Hsa-miR-27a-5p expression in breast cancer and its association with patient outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1492.