A microRNA signature associated with pathological complete response to novel neoadjuvant therapy regimen in triple-negative breast cancer

Abstract

Neoadjuvant chemotherapy aims to improve the outcome of breast cancer patients, but only few would benefit from this treatment. Pathological complete response has been proposed as a surrogate marker for the prediction of long-term clinical benefits; however, 50%-85% patients have an unfavorable pathological complete response to chemotherapy. MicroRNAs are known biomarkers of breast cancer progression; nevertheless, their potential to identify patients with pathological complete response remains poorly understood. Here, we investigated whether a microRNA profile could be associated with pathological complete response in triple-negative breast cancer patients receiving 5-fluorouracil, adriamycin, cyclophosphamide-cisplatin/paclitaxel as a novel neoadjuvant chemotherapy. In the discovery cohort, the expression of 754 microRNAs was examined in tumors from 10 triple-negative breast cancer patients who achieved pathological complete response and 8 without pathological complete response using TaqMan Low-Density Arrays. Unsupervised hierarchical cluster analysis identified 11 microRNAs with significant differences between responder and no-responder patients (fold change ≥ 1.5; p < 0.05). The differential expression of miR-30a, miR-9-3p, miR-770, and miR-143-5p was validated in an independent group of 17 patients with or without pathological complete response. Moreover, Kaplan-Meier analysis showed that expression of these four microRNAs was associated with an increased disease-free survival. Gene ontology classification of predicted microRNA targets indicated that numerous genes are involved in pathways related to chemoresistance, such as vascular endothelial growth factor, focal adhesion kinase, WNT, ERbB, phosphoinositide 3-kinase, and AKT signaling. In summary, we identified a novel microRNA expression signature associated with pathological complete response in breast cancer. We propose that the four validated microRNAs could be used as molecular biomarkers of clinical response in triple-negative breast cancer patients with pathological complete response to neoadjuvant therapy.

<p>Mirna21 Expression in the Breast Cancer Tumor Tissue is Independent of Neoadjuvant Chemotherapy</p>

“…Previous studies reported on the roles of the expression of certain miRNAs, such as miRNA-18a, miRNA-7 and miRNA-340, in the tumor tissue of patients who achieved PCR in predicting survival outcomes and response to chemotherapy. [24][25][26][27] The association between miRNA-21 expression and clinicopathological features in our study demonstrated an upregulation of this biomarker for clinical stages II and III, axillary lymph node metastasis and all breast cancer subtypes regardless of previous treatment with NAC. Conversely, there were no significant correlations of miRNA-21 expression with tumor size or tumor histological grade, which is in accordance with the findings of previous reports.…”

Exploring specific prognostic biomarkers in triple-negative breast cancer

“…As for miR-9-3p, although less intensively investigated in breast cancer, it has been identified as a tumor suppressor in claudin-low breast cancer cells 44 . Moreover, downregulation of miR-9-3p was reported to be related to worse clinical chemotherapy response in breast cancer 45 . However, the specific role of miR-9-3p in TNBC remains unknown.…”

Prolactin-Responsive Circular RNA circHIPK3 Promotes Proliferation of Mammary Epithelial Cells from Dairy Cow

“…One of the identified miRNAs, miR-134-5p, was reported in rats to exhibit a significantly down-regulated expression after seven days of lactation compared with the expression level on the first day of lactation [33]. Another miRNA, miR-143-5p, is down-regulated in breast cancer [34]. Thus, miR-134-5p and miR-143-5p have the potential to be bound by circHIPK3 and have functions related to breast function and lactation, so these should be further investigated as targets of circHIPK3 that potentially explain its role in breast development or diseases.…”