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The American Society of Breast Surgeons.
Annals of Surgical Oncology

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Novel MicroRNA-Based Risk Score Identified by Integrated Analyses to Predict Metastasis and Poor Prognosis in Breast Cancer

Tstutomu Kawaguchi MD, PhD, Li Yan PhD, Qianya Qi MS, Xuan Peng MS, Stephen B. Edge MD, Jessica Young MD, Song Yao PhD, Song Liu PhD, Eigo Otsuji MD, PhD, Kazuaki Takabe MD, PhD, FACS
Translational Research and Biomarkers
Volume 25, Issue 13 / December , 2018

Abstract

Background

The use of biomarkers that allow early therapeutic intervention or intensive follow-up evaluation is expected to be a powerful means for reducing breast cancer mortality. MicroRNAs (miRNAs) are known to play major roles in cancer biology including metastasis. This study aimed to develop a novel miRNA risk score to predict patient survival and metastasis in breast cancer.

Methods

An integrated unbiased approach was applied to derive a composite risk score for prognosis based on miRNA expression in primary breast tumors in 1051 breast cancer patients from The Cancer Genome Atlas (TCGA). Further analysis of the risk score with metastasis/recurrence was performed using the TCGA data set and validated in a separate patient population using small RNA sequencing.

Results

The three-miRNAs risk score (miR-19a, miR-93, and miR-106a) was developed using the TCGA cohort, which predicted poor prognosis (p = 0.0005) independently of known clinical risk factors. The prognostic value was validated in another three following independent cohorts: GSE19536 (p = 0.0009), GSE22220 (p = 0.0003), and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (p = 0.0023). The three-miRNAs risk score predicted bone recurrence in TCGA (p = 0.0052), and the findings were validated in another independent population of patients who experienced bone recurrence and age/stage-matched patients without any recurrence. The three-miRNAs risk score enriched multiple metastasis-related gene sets such as angiogenesis and epithelial mesenchymal transition in a gene-set-enrichment analysis.

Conclusions

The authors developed the novel miRNA-based risk score, which is a promising biomarker for prediction of worse survival and bone recurrence potential in breast cancer.

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