Research Paper Volume 11, Issue 2 pp 649—662

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

Jianguo Lai 1, 2, , Hongli Wang 1, 2, , Zihao Pan 1, 3, , Fengxi Su 1, 2, ,

  • 1 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
  • 2 Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
  • 3 Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

received: October 30, 2018 ; accepted: January 5, 2019 ; published: January 30, 2019 ;

https://doi.org/10.18632/aging.101767
How to Cite

Copyright: Lai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.

Abbreviations

TNM: tumor-node-metastasis; OS: overall survival; BC: breast cancer; miRNA: microRNA; DEMs: differentially expressed miRNAs; TCGA: The Cancer Genome Atlas; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes analysis; IQR: interquartile range; MF: molecular function; BP: biological process; CC: cellular component; ER: estrogen receptor; PR: progestrone receptor; HER2: human epithelial growth factor receptor 2; AUC: the area under the curve; ROC: receiver operating characteristic; DAVID: the Database for Annotation, Visualization, and Integrated Discovery 6.8 Bioinformatics Tool; CPHR: Cox proportional hazards regression.