The use of miRNAs in predicting response to neoadjuvant chemotherapy in Triple Negative Breast Cancer (TNBC)

Abstract

Breast cancer is the most common malignancy in women. Triple-negative breast cancer (TNBC) is an aggressive subtype that accounts for 10-15% of all cases, and the disease is associated with high invasiveness, metastasis, and susceptibility to relapse. Due to the absence of estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors in TNBC, endocrine and molecular targeted therapies are ineffective. Neoadjuvant chemotherapy, the primary treatment option, is only effective in ~50% of patients. MicroRNAs (miRNAs) are small non-coding RNA molecules whose dysregulation can alter the expression of specific genes, affecting cancer pathogenesis. This research aimed to identify whether microRNAs can be used as noninvasive biomarkers to predict a patient’s response to chemotherapy. First, bioinformatic case study analysis of the cancer genome atlas (TCGA) datasets revealed 195 differentially expressed miRNAs targeting 57 genes linked to the platinum drug resistance pathway. Analysis of patient survival data showed 13 of those to be directly related to patient survival rate. Subsequently, we selected four different miRNAs for quantitative reverse transcription PCR verification in specimens from patients with TNBC undergoing neoadjuvant chemotherapy. Finally, we conducted a statistical analysis to evaluate the candidate miRNAs’ relation with the overall or progression-free survival of TNBC patients.