Diagnostic and prognostic implications of a serum miRNA panel in oesophageal squamous cell carcinoma

PLoS One. 2014 Mar 20;9(3):e92292. doi: 10.1371/journal.pone.0092292. eCollection 2014.

Abstract

Background and aim: Circulating microRNAs (miRNAs) are potential biomarkers for cancer detection; however, little is known about their prognostic impact on oesophageal squamous cell carcinoma (ESCC). The current study aims to uncover novel miRNAs for prognostic biomarkers in ESCC patients.

Patients and methods: We initially screened the expression of 754 serum miRNAs using TaqMan Low Density Array in two pooled samples respectively from 28 ESCC and 28 normal controls. Markedly upregulated miRNAs in ESCC and some miRNAs reported to be differently expressed in ESCC tissue were then validated individually by RT-qPCR in another 83 patients and 83 controls arranged in two phases. The changes of the selected miRNAs during the esophagectomy and their prognostic value were examined.

Results: Seven serum miRNAs were found to be significantly higher in ESCC than in controls; namely, miR-25, miR-100, miR-193-3p, miR-194, miR-223, miR-337-5p and miR-483-5p (P<0.0001), and the area under the receiver-operating-characteristic (ROC) curve (AUC) for the seven-miRNA panel was 0.83 (95% CI 0.75-0.90). Most of these miRNAs declined markedly in postoperative samples versus preoperative samples (P<0.05). Moreover, high level of miR-25 was significantly correlated with shorter overall survival in patients (P = 0.027). Cox regression analysis identified lymph node metastasis, miR-25 and miR-100 as the independent risk factors for overall survival (hazard ratio (HR) 2.98 [1.36-6.55], P = 0.006; HR 3.84 [1.02-14.41], P = 0.029; HR 4.18 [1.21-14.50], P = 0.024, respectively).

Conclusion: The seven serum miRNAs could potentially serve as novel biomarkers for ESCC; moreover, specific miRNAs such as miR-25 and miR-100 can predict poor survival in ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / blood*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / surgery
  • Case-Control Studies
  • Demography
  • Esophageal Neoplasms / blood*
  • Esophageal Neoplasms / diagnosis
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / surgery
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • ROC Curve
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors

Substances

  • MicroRNAs

Grants and funding

This work was supported by grants from the National Basic Research Program of China (973 Program) (no. 2014CB542300), the National Natural Science Foundation of China (Nos. 81171661, 81301511 and 81271904), Natural Science Foundation of Jiangsu Province (no. BK2011013), Medical Scientific Research Foundation of Nanjing Military Command (no. 12Z28) and the Research Special Fund for Public Welfare Industry of Health (no. 201302018). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.