Prognostic role of microRNA 182 and microRNA 18a in locally advanced triple negative breast cancer

Abstract

Background The study assessed the epigenetic regulation and the role of microRNA (miR) expression in locally advanced triple negative breast cancers (TNBC) and comparison with the clinico-pathological variables and survival. Methods Fifty patients of locally advanced TNBC during the period 2011–2013 were included. Expression level of test microRNA (miR-182 and miR-18a) was determined using Taqman quantitative Real time polymerase chain reaction (qRT-PCR) from formalin fixed paraffin embedded biopsy blocks. Clinical and demographic information and survival data was retrieved from the Hospital medical records. Results An improved clinical complete response (cCR) was observed in patients with age ≥ 45 years (80%), premenopausal status (70%), tumor size < 6 cms (80%), nodal status N0-N1 (95%) and grade II-III tumor (80%). A statistically significant correlation was observed on comparison of cCR with menopausal status (p-value 0.020), T category (p-value 0.018) and the clinical nodal status (p-value 0.003). pCR also correlated with clinical nodal status (p-value 0.008). Epigenetically, miR-18a under expression (< 8.84) was most commonly associated with tumor size < 6 cms (76.7%), clinical nodal status N0-N1 (90%), cCR (60%) and pCR (53.3%). A similar trend was observed with miR-182. Statistical significance was observed with T category (p-values 0.003 and 0.004), clinical nodal status (p-values 0.001 and 0.001), clinical response (p-values 0.002 and 0.002) and pathological response (p-values 0.007 and 0.006) with respect to miR-18a and miR-182, respectively. Also, the menopausal status significantly correlated with the miR-182 expression (p-value 0.009). miR-182 overexpression (≥ 6.32) was not observed in any of the postmenopausal patients. A univariate cox proportional hazard regression model also showed statistical interactions (p-values <0.004). Conclusion miR-182 and miR-18a overexpression correlates with worse clinical and pathological tumor characteristics in locally advanced TNBC and hence could be used to predict the outcomes and prognosis in these patients.

Investigation of BRCAness associated miRNA-gene axes in breast cancer: cell-free miR-182-5p as a potential expression signature of BRCAness

“…The clinicopathologic analyses revealed that the expression level of miR-182-5p associates with larger tumor size, lymph node metastasis, and higher histologic grade in the BC patients. These results, in accordance with previous reports [ 46 – 48 ], imply the oncogenic roles of miR-182-5p in BC.…”

Breast cancer cell-derived extracellular vesicles transfer miR-182-5p and promote breast carcinogenesis via the CMTM7/EGFR/AKT axis

“…Meanwhile, miR-182-5p could promote the proliferation, migration and angiogenesis of HUVECs. Consistently, the expression of miR-182 has shown a dramatic overexpression in breast cancer tissue samples (Barsoum et al 2020 ), and moreover, its overexpression significantly relates to poor clinical and pathological tumor characteristics in patients with locally advanced triple negative breast cancer and thus can be used as a tool to predict the outcomes and prognosis in these patients (Bajaj 2020 ). Downregulation of miR-182-5p contributes to inhibition of cell proliferation and promotion of tumor cell apoptosis by impairing the TLR4/NF-κB signaling pathway activity and increasing FBXW7 expression (Wu et al 2020 ).…”

Clinical Value and Molecular Function of Circulating MicroRNAs in Endometrial Cancer Regulation: A Systematic Review

“…The information about the reproducibility of serum or plasma analysis is inconsistent. The study by Mitchell et al suggests that the quantification of miRs in plasma and serum are correlated and that the analysis of miRs from plasma or serum are therefore reliable sources of sampling [ 52 ]. However, other studies have shown that miR expression is different according to the origin of the sample (plasma or serum).…”

“…MiRs have been proven to be stable markers and resistant to RNase activity and environmental factors. In a study by Mitchell et al [ 52 ], miR levels did not change when modifying the temperature of the samples (room temperature incubation for up to 24 h or freeze–thawing for up to 8 cycles). It was also shown that endogenous miRs were resistant to RNase activity, whereas exogenous miRs were rapidly degraded when introduced.…”