Association of microRNAs and pathologic response to preoperative chemotherapy in triple negative breast cancer: preliminary report

Abstract

Triple negative breast cancer (TNBC) has caught the attention of oncologists worldwide because of poor prognosis and paucity of targeted therapies. Gene pathways have been widely studied, but less is known about epigenetic factors such as microRNAs (miRNAs) and their role in tailoring an individual systemic and surgical approach for breast cancer patients. The aim of the study was to examine selected miRNAs in TNBC core biopsies sampled before preoperative chemotherapy and the subsequent pathologic response in mastectomy or breast conservation specimens. Prior to treatment, core needle biopsies were collected from 11 female patients with inoperable locally advanced TNBC or large resectable tumors suitable for down-staging. In all 11 TNBC core biopsies we analyzed 19 miRNAs per sample: 512, 190, 200, 346, 148, 449, 203, 577, 93, 126, 423, 129, 193, 182, 136, 135, 191, 122 and 222 (miRCURY LNA™ Universal RT microRNA polymerase chain reaction Custom Pick & Mixpanels). The Wilcoxon signed-rank test was used to compare related samples. Ingenuity pathway analysis was used to evaluate potential functional significance of differentially expressed miRNAs. Statistical analysis showed that 3 of 19 miRNAs differed in relation to pathologic response i.e. good versus poor. These differences failed to reach statistical significance, although a trend was observed (p = 0.06). Among these miRNAs, we identified—miR-200b-3p, miR-190a and miR-512-5p. In summary, our results indicate that higher miR-200b-3p, higher miR-190a and lower miR-512-5p expression levels in core biopsies sampled from TNBC patients may be associated with better pathologic response to chemotherapy and the increased feasibility of breast conserving surgery in these patients. Although these results were from a small cohort, they provide an important basis for larger, prospective, multicenter studies to investigate the potential role of miRNAs in neoadjuvant setting.

Candidate diagnostic miRNAs that can detect cancer in prostate biopsy

“…Many miRNAs identified as dysregulated in the present study have also been reported as altered in other cancer types, including breast cancer (miR‐374b‐5p, miR‐429, miR‐200b‐5p, miR‐200b‐3p, miR‐187‐3p, miR‐196a‐5p, miR‐183‐5p, miR‐21‐5p, and miR‐182‐5p); gastric cancer (miR‐374b‐5p, miR‐200c‐3p, miR‐18b‐5p, miR‐196a‐5p, miR‐21‐5p, and miR‐20a‐3p); ovarian cancer (miR‐141‐5p, miR‐182‐5p, miR‐483‐3p, and miR‐200c‐3p); hepatocellular carcinoma (miR‐135a‐5p, miR‐187‐3p, miR‐148a‐5p, miR‐200a‐3p, and miR‐9‐3p); colorectal cancer (miR‐9‐3p, miR‐135a‐5p, miR‐200c‐3p, miR‐200b‐3p, and miR‐182‐5p); thyroid cancer (miR‐7‐5p and miR‐9‐3p); lung cancer (miR‐200b‐5p, miR‐200b‐3p, miR‐9‐5p, miR‐200a‐3p, and miR‐21‐5p); pancreatic cancer (miR‐200b‐3p, miR‐483‐3p, and miR‐183‐5p); chronic lymphocytic leukemia (miR‐4521, miR‐7‐5p, and miR‐182‐5p); Hodgkin lymphoma (miR‐876‐5p); cervical cancer (miR‐429); head and neck squamous cell carcinoma (miR‐200b‐5p); and bladder cancer (miR‐148a‐3p) …”

MicroRNAs in regulation of triple-negative breast cancer progression

“…Overexpression of miR-200c in TNBC cells (MDA-MB-231 cell line) resulted in loss of the elongated shape associated with a motile, mesenchymal phenotype and acquisition of the epithelial-like morphology. Downregulation of miR-200b was found crucial in increase of EMT in TNBC cells by targeting ZEB1/2 and suppressing PKCα (Kolacinska et al 2014; Humphries et al 2014; Rhodes et al 2015). Loss of the actin-based structure was orchestrated by miR-200c, which directly targeted actin regulatory proteins, FHOD1 and PPM1F, in a ZEB1/2-independent manner and led to the inhibition of migration and invasion of the cells (Jurmeister et al 2012).…”

Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer

“…The predictive and prognostic value of miRNAs has been investigated in breast cancer . In a small study (n = 11), Kolacinska et al found higher expression of miR‐200b‐3p/miR‐190a along with lower expression of miR‐512‐5p in breast cancer tissue before chemotherapy correlated with a better pathologic response to NCT. Wang et al proposed circulating miR‐125b as a marker predicting chemo‐resistance in breast cancer.…”