Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer

Acta Oncol. 2015;54(9):1582-91. doi: 10.3109/0284186X.2015.1064161.


Background: MicroRNAs (miRNAs) have been associated with prognosis in esophageal cancer, suggesting a role for miRNAs to help guide treatment decisions. Especially, miR-21 and miR-375 have been investigated as prognostic biomarkers. The aim of this study was to evaluate the prognostic potential of miR-21 and miR-375 in primary esophageal squamous cell carcinomas (ESCC) and esophagogastric adenocarcinomas (EAC).

Material and methods: Pre-therapeutic tumor specimens from 195 patients with loco-regional esophageal cancer treated with neoadjuvant or definitive chemoradiotherapy or perioperative chemotherapy were analyzed. Expression levels of miR-21 and miR-375 were quantified using Affymetrix GeneChip miRNA 1.0 Array. The Cox proportional hazards model was used to assess the correlation of miR-21 and miR-375 with disease-specific survival (DSS) and overall survival (OS). Forest plots were performed to evaluate the prognostic impact of miR-21 and miR-375 in the present study and previously published reports.

Results: In ESCC, patients with miR-21 expression levels above median showed a trend towards poorer DSS and OS. When dividing miR-21 expression by tertiles, high levels of miR-21 significantly correlated with shortened DSS [HR 1.76 (95% CI 1.05-2.97) but not OS. Similarly for EAC, a significant association between miR-21 expression above median and DSS was observed [HR 3.37 (95% CI 1.41-8.05)], in addition to a trend towards poorer OS for patients with miR-21 expression above median. Multivariate analyses identified miR-21 as an independent prognostic marker for DSS in EAC [HR 3.52 (95% CI 1.06-11.69)]. High miR-375 was not correlated with improved prognosis in either histology. However, Forest plots demonstrated that both miR-21 and miR-375 were of prognostic impact in ESCC.

Conclusion: In this study, miR-21 was identified as an independent prognostic biomarker for DSS in patients with EAC whereas miR-21 failed to show independent prognostic significance in ESCC. High miR-375 was not associated with enhanced survival in either histology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy, Adjuvant
  • Esophageal Neoplasms / diagnostic imaging
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / therapy
  • Esophagectomy
  • Female
  • Gene Expression
  • Humans
  • Male
  • MicroRNAs / analysis*
  • Middle Aged
  • Neoadjuvant Therapy
  • Prognosis
  • Proportional Hazards Models
  • Radiography
  • Retrospective Studies
  • Survival Rate


  • Biomarkers, Tumor
  • MIRN21 microRNA, human
  • MIRN375 microRNA, human
  • MicroRNAs