Prognostic and diagnostic potential of miR-146a in oesophageal squamous cell carcinoma

Br J Cancer. 2016 Feb 2;114(3):290-7. doi: 10.1038/bjc.2015.463. Epub 2016 Jan 21.

Abstract

Background: Accumulating evidence indicates that dysregulated microRNA-146a (miR-146a) is involved in tumour genesis and cancer progression. We aimed to evaluate its expression level and the potential for the diagnosis and prognosis in oesophageal squamous cell cancer (ESCC).

Methods: We examined miR-146a expression in 62 pairs of ESCC cancerous and matched paracancerous tissue, 115 formalin-fixed paraffin-embedded (FFPE) tissue samples and serum samples from 154 ESCC patients and 154 healthy volunteers using quantitative reverse transcription-PCR (qRT-PCR). Kaplan-Meier method, Cox regression and receiver-operating characteristic (ROC) curve analysis were applied to analyse its prognostic and diagnostic value.

Results: MicroRNA-146a expression level was significantly decreased in ESCC tissue compared with paracancerous tissue (P<0.001). Its regulation level was negatively associated with T factor and TNM stage. Kaplan-Meier curve revealed that its downregulation level predicted worse overall survival (OS) and progression-free survival (PFS). Both univariate and multivariate analyses identified miR-146a expression as independent prognostic factor for OS and PFS. Serum miR-146a was significantly reduced in ESCC patients than in healthy controls (P<0.001). Area under the curve ROC value, sensitivity and specificity for this marker were 0.863 ± 0.033, 85.7% and 68.6% in the Discovery Group, and 0.891 ± 0.027, 82.1% and 83.3% in the Validation Group.

Conclusions: MicroRNA-146a is significantly reduced in cancerous tissue and serum samples of ESCC patients. It is an ideal biomarker for the prognosis and diagnosis of ESCC.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Disease-Free Survival
  • Esophageal Neoplasms / diagnosis
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • MIRN146 microRNA, human
  • MicroRNAs