4.6 Article

A novel six-microRNA-based model to improve prognosis prediction of breast cancer

Journal

AGING-US
Volume 11, Issue 2, Pages 649-662

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/aging.101767

Keywords

breast cancer; microRNA; nomogram; survival; model

Funding

  1. National Natural Science Foundation of China [81402201, 81372817]
  2. National Natural Science Foundation of Guangdong Province [2014A030310070]
  3. Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of the Guangzhou Bureau of Science and Information Technology [163]

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Current tumor-node-metastasis (TNM) stage is unable to accurately predict the overall survival (OS) in breast cancer (BC) patients. This study aimed to construct a microRNA (miRNA)-based model to improve survival prediction of BC. We confirmed 99 differentially expressed miRNAs (DEMs) in 1044 BC samples compared to 102 adjacent normal breast tissues from The Cancer Genome Atlas (TCGA) database. Prognostic DEMs were used to establish a miRNA-based nomogram via Cox regression model. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses (KEGG) were executed to analyze target genes of miRNAs. A six-miRNA signature was screened to effectively distinguish high-risk patients in the primary and validation cohort (all P<0.001). Furthermore, we established a novel prognostic model incorporating the six-miRNA signature and clinical risk factors to predict 5-year OS of BC. Time-dependent receiver operating characteristic analysis suggested that the predictive accuracy of the six-miRNA-based nomogram was distinctly higher than that of TNM stage (0.758 vs 0.650, P<0.001). GO and KEGG pathway analyses showed that the 39 target genes mainly enrichment in protein binding, cytoplasm and MAPK signaling pathway. Our six-miRNA-based model is a reliable prognostic tool for survival prediction and provides information for individualized treatment decisions in BC patients.

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