The Role of miR-375-3p, miR-210-3p and Let-7e-5p in the Pathological Response of Breast Cancer Patients to Neoadjuvant Therapy

Abstract

Background and Objectives: Prediction of response to therapy remains a continuing challenge in treating breast cancer, especially for identifying molecular tissue markers that best characterize resistant tumours. Microribonucleic acids (miRNA), known as master modulators of tumour phenotype, could be helpful candidates for predicting drug resistance. We aimed to assess the association of miR-375-3p, miR-210-3p and let-7e-5p in breast cancer tissues with pathological response to neoadjuvant therapy (NAT) and clinicopathological data. Material and methods: Sixty female patients diagnosed with invasive breast cancer at The Oncology Institute “Ion Chiricuță”, Cluj-Napoca, Romania (IOCN) were included in this study. Before patients received any treatment, fresh breast tissue biopsies were collected through core biopsy under echographic guidance and processed for total RNA extraction and miRNA quantification. The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) database was used as an independent external validation cohort. Results: miR-375-3p expression was associated with more differentiated tumours, hormone receptor presence and lymphatic invasion. According to the Miller–Payne system, a higher miR-375-3p expression was calculated for patients that presented with intermediate versus (vs.) no pathological response. Higher miR-210-3p expression was associated with an improved response to NAT in both Miller–Payne and RCB evaluation systems. Several druggable mRNA targets were correlated with miR-375-3p and miR-210-3p expression, with upstream analysis using the IPA knowledge base revealing a list of possible chemical and biological targeting drugs. Regarding let-7e-5p, no significant association was noticed with any of the analysed clinicopathological data. Conclusions: Our results suggest that tumours with higher levels of miR-375-3p are more sensitive to neoadjuvant therapy compared to resistant tumours and that higher miR-210-3p expression in responsive tumours could indicate an excellent pathological response.

Identification of exosomal microRNAs and related hub genes associated with imatinib resistance in chronic myeloid leukemia

“…Oncogenic activity has been reported for this miRNA in the progression of lung and endometrial carcinoma (Han et al 2020;Dai et al 2022). On the other hand, in a study, it was reported that the desired pathological response was achieved with high expression of miR-210-3p in breast cancer (Lisencu et al 2022). These studies collectively reported the different activities of miR-210-3p in different cancer types.…”

Potential Impact of Preoperative Circulating Biomarkers on Individual Escalating/de-Escalating Strategies in Early Breast Cancer

“…More and more ncRNA have been cataloged and connected to the prediction of treatment response in eBC [183][184][185]. However, low sensitivity and low specificity of detection techniques limit miRNA analysis, and new methods are under development.…”

Advances in Cancer Therapy from Research to Clinical Practice—Surgical, Molecular or Systemic Management of Cancer

“…For breast cancer, for example, Lisencu et al [ 5 ] tried to determine molecular predictive factors which are linked to the probability of obtaining a pathological response to neoadjuvant treatment. Selecting early those patients with the best chance of responding to a selective (and costly) therapy remains a challenging task.…”