MicroRNAs involved in immune response as prognostic markers in early and metastatic breast cancer.

Abstract

e15528 Background: MicroRNAs (miRNAs) are involved in the regulation of immune response and have an important role in immune escape. We analyzed the expression levels of plasma miR-10b, miR-126, miR-19α, miR-20α and miR-155, which regulate tumor-immune interactions and investigated their prognostic implications in patients with early (eBC) and metastatic (mBC) breast cancer. Methods: Blood samples were obtained before treatment from 140 and 64 patients with eBC and mBC, respectively. Plasma miRNA expression levels were assessed by qRT-PCR and expression was classified as high or low according to the median values. Results: A panel of four miRNAs (miR-19a, miR-20a, miR-126 and miR-155) could discriminate eBC from mBC (AUC 0.802, p < 0.001). In early disease, miR-10b (p = 0.022) and miR-155 (p = 0.005) expression was lower in relapsed (n = 46) compared to non-relapsed (n = 94) patients; miR-155 expression along with lymph node infiltration and tumor grade had increased ability to predict relapse (AUC = 0.775; p = 0.003). In addition, miR-10b (p = 0.015), miR-19a (p = 0.003), miR-20a (p = 0.012), miR-126 (p = 0.001) and miR-155 (p < 0.001) expression levels were lower in patients with early relapse (relapse at ≤2 years). MiR-155 and miR-19a had the highest performance in discriminating early relapse (AUC 0.855; p < 0.001 and AUC = 0.729; p = 0.003, respectively), whereas, combined mir-155 and miR-19a expression further increased the accuracy of prediction (AUC = 0.867; p < 0.001). In eBC, the number of infiltrated lymph nodes and low miR-10b independently predicted for shorter DFS (p = 0.001 and p = 0.03, respectively) and axillary lymph nodes for shorter OS (p = 0.003). In the triple negative subgroup, low miR-155 strongly predicted for shorter DFS (p = 0.037). In mBC, recurrent disease and low miR-10b expression independently predicted for shorter PFS (p = 0.001 and p = 0.017, respectively), whereas performance status of 2 independently predicted for shorter OS (p = 0.03). Conclusions: Deregulated expression of circulating miRNAs involved in tumor-immune interactions can discriminate disease status in BC and independently predicts for patients’ outcome in early and mBC. Our results further support the notion that circulating miRNAs represent a useful prognostic tool in patients with BC.

MicroRNAs Regulating Tumor Immune Response in the Prediction of the Outcome in Patients With Breast Cancer

“…We herein show that low plasma miR-10b expression was a predictor for shorter DFS in eBC and for shorter PFS in mBC patients. Furthermore results from our lab showed that the expression levels of miR-10b in the plasma were lower in relapsed compared to non-relapsed eBC patients ( Papadaki et al, 2020b ). Our findings suggest that high miR-10b expression levels in the plasma could reflect effective tumor-immune cell interactions in the TME associated with favourable patients’ outcomes.…”

“…We have previously shown that the above miRNAs are differentially expressed among healthy women and eBC patients ( Papadaki et al, 2020b ). In addition, a differential expression pattern was encountered among relapsed and non-relapsed patients with early disease ( Papadaki et al, 2020b ).…”

“…We have previously shown that the above miRNAs are differentially expressed among healthy women and eBC patients ( Papadaki et al, 2020b ). In addition, a differential expression pattern was encountered among relapsed and non-relapsed patients with early disease ( Papadaki et al, 2020b ). Based on the above evidence indicating an association of these miRNAs with disease progression, we hypothesized that the expression of miR-10b, miR-19a, miR-20a, miR-126, and miR-155 in the plasma may differ among patients with eBC and mBC and that their expression is associated with significant prognostic implications in the early and/or metastatic disease stage.…”

Extracellular Vesicles in Breast Cancer: From Biology and Function to Clinical Diagnosis and Therapeutic Management

“…Seven miRNAs were differentially expressed between BC patients with and without recurrences, including four miRNAs upregulated (miR-21-5p, miR-375, miR-205-5p, and miR-194-5p) and three miRNAs downregulated (miR-382-5p, miR-376c-3p, and miR-411-5p) [ 456 ]. The association of miR-19a, miR-20a, miR-126, and miR-155 can discriminate against the metastatic outcome of BC patients [ 457 , 458 ].…”