A panel of eight microRNAs is a good predictive parameter for triple-negative breast cancer relapse

Abstract

Rationale: Triple-negative breast cancer (TNBC), which has the highest recurrence rate and shortest survival time of all breast cancers, is in urgent need of a risk assessment method to determine an accurate treatment course. Recently, miRNA expression patterns have been identified as potential biomarkers for diagnosis, prognosis, and personalized therapy. Here, we investigate a combination of candidate miRNAs as a clinically applicable signature that can precisely predict relapse in TNBC patients after surgery. Methods: Four total cohorts of training (TCGA_TNBC and GEOD-40525) and validation (GSE40049 and GSE19783) datasets were analyzed with logistic regression and Gaussian mixture analyses. We established a miRNA signature risk model and identified an 8-miRNA signature for the prediction of TNBC relapse. Results: The miRNA signature risk model identified ten candidate miRNAs in the training set. By combining 8 of the 10 miRNAs (miR-139-5p, miR-10b-5p, miR-486-5p, miR-455-3p, miR-107, miR-146b-5p, miR-324-5p and miR-20a-5p), an accurate predictive model of relapse in TNBC patients was established and was highly correlated with prognosis (AUC of 0.80). Subsequently, this 8-miRNA signature prognosticated relapse in the two validation sets with AUCs of 0.89 and 0.90. Conclusion: The 8-miRNA signature predictive model may help clinicians provide a prognosis for TNBC patients with a high risk of recurrence after surgery and provide further personalized treatment to decrease the chance of relapse.

Extracellular MicroRNAs as Intercellular Mediators and Noninvasive Biomarkers of Cancer

“…Under pathological conditions, alterations in the miRNA expression levels are associated with a wide range of diseases, including cancer [ 82 , 83 , 84 ]. Furthermore, the in vitro and in vivo studies of disease-associated endogenous miRNAs have demonstrated their participation in the oncogenesis and tumor progression mechanisms in several cancers [ 85 , 86 , 87 , 88 ].…”

Novel miRNA Targets and Therapies in the Triple-Negative Breast Cancer Microenvironment: An Emerging Hope for a Challenging Disease

“…It is reasonable to hypothesize that tumor evolution subsequent to tumor initiation is driven by selection of miRNA post-translational regulatory programs that favor proliferation, migration, invasion and metastasis. The prognostic implications of such tumor progression supporting programming is reflected in the discovery of a panel of miRNAs with prognostic predictive value in TNBC [ 103 ]. Specifically, the expression of eight miRNAs (miR-139-5p, miR-10b-5p, miR-486-5p, miR-455-3p, miR-107, miR-146b-5p, miR-324-5p and miR-20a-5p) was found to predict post-surgical relapse in TNBC patients.…”

“…Of all associated miRNAs, miR-139-5p showed the strongest correlation with disease free survival and TNM stage, although all associations with overall survival were weaker. Tumor suppressive function of miR-139 may involve regulation of targets including VEGFR, IGF-1R, HOXA10, Wnt, Ras, PI3K, NFκB and ROCK2 [ 103 , 104 ]. LOX, which is involved in collagen crosslinking, is targeted by miR-142.3p along with HIF1α and integrin subunit alpha 5 (ITGA5), thereby overcoming chemoresistance in TNBC [ 86 ].…”

Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype

“…Transcriptomic analysis provided the complex mRNAs and noncoding RNA expression patterns, which enables interpretation of the cell genomic codex. Applied to TNBC, it identifies deregulated miRNA expression patterns playing different roles as anti-oncomiR or oncomiR in tumor development, defining miRNA signatures related to prognosis [69,70] and stratification of TNBC into subclasses [71].…”