Low Expression of Circulating MicroRNA-34c is Associated with Poor Prognosis in Triple-Negative Breast Cancer

Yonsei Med J. 2017 Jul;58(4):697-702. doi: 10.3349/ymj.2017.58.4.697.

Abstract

Purpose: The microRNA-34 (miR-34) family is important in tumor regulation. This study aimed to investigate the association of circulating miR-34 family proteins with clinicopathological features and their prognostic value in triple-negative breast cancer (TNBC) patients.

Materials and methods: In this cohort study, 173 TNBC patients admitted to First People's Hospital of Shunde from May 1, 2009 to April 30, 2013 were enrolled. Meanwhile, 75 age-matched healthy women volunteers were identified as healthy controls (HCs). We examined the expression of miR-34 family (miR-34a/b/c) proteins in plasma collected from TNBC patients before any treatment was performed and from age-matched HCs using qPCR methods.

Results: The expressions of miR-34a/34b/34c were significantly lower in TNBC patients than in HC (p<0.001, p=0.027, p<0.001, respectively). miR-34a was correlated with tumor grade (p=0.038), lymph node positive (p=0.027), distant metastasis (p=0.004), and surgery (p=0.023); miR-34b was correlated with lymph node positivity (p=0.027); and miR-34c was correlated with tumor grade (p=0.017) and distant metastasis (p<0.001). Kaplan-Meier curve analysis displayed low expression of miR-34a as associated with worse overall survival (OS) (p=0.011), as well as miR-34c low expression (p=0.002). In addition, univariate and multivariate Cox proportional hazards regression was performed, and low expression of miR-34c (p=0.011) was found to be an independent risk factor for OS, as well as tumor grade (p=0.013), lymph node positive (p=0.050), and distant metastasis (p=0.021).

Conclusion: In conclusion, this study demonstrated reduced miR-34a/c expression is highly associated with tumor progression and indicated worse prognosis. Also, miR-34c was an independent risk factor for OS in TNBC patients.

Keywords: Circulating microRNA; miR-34 family; triple-negative breast cancer.

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Factor Analysis, Statistical
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / blood*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • Triple Negative Breast Neoplasms / blood*
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology

Substances

  • MIRN34 microRNA, human
  • MicroRNAs