Combined identification of three miRNAs in serum as effective diagnostic biomarkers for HNSCC

EBioMedicine. 2019 Dec:50:135-143. doi: 10.1016/j.ebiom.2019.11.016. Epub 2019 Nov 26.

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is a disastrous disease with substantial morbidity and mortality. This study aims to explore the effective diagnostic and prognostic biomarkers for HNSCC.

Methods: MiRNA expression data and corresponding clinical information of HNSCC from The Cancer Genome Atlas (TCGA) database were analyzed comprehensively to identify the miRNAs with diagnostic and prognostic power. The predictive ability of different classifications was analyzed for the three-miRNA combinations. Diagnostic and prognostic value were then evaluated and verified in clinical patients.

Findings: 128 differentially expressed miRNAs in HNSCC tissues were identified in the TCGA dataset, and 10 miRNAs were finally selected for further study. Classification analysis developed a three-miRNA signature of hsa-mir-383, hsa-mir-615, and hsa-mir-877 with the best diagnosis power, which was verified in validation patients. Survival analysis indicated that different expression levels of hsa-mir-383, rather than that of hsa-mir-615 or hsa-mir-877 led to significantly different survival rates in both cohorts. Furthermore, the multivariate Cox hazards analysis suggested that the microRNA signature yielded statistical significance to predict clinical outcome independently from other clinical variables in validation patients.

Interpretation: A three-miRNA signature of hsa-mir-383, hsa-mir-615, and hsa-mir-877 may serve as an excellent diagnostic biomarker for HNSCC, and potential prognostic significance for HNSCC patients.

Funding: This work was supported by the grants of the National Natural Science Foundation of China (81901021), Key Research and Development Program of Shandong (2019GSF108277), China postdoctoral Scinence Foundation Grant (2019M652380), Fundamental Research Funds of Shandong University (2018CJ047).

Keywords: Biomarker; Diagnosis; Head and neck squamous cell carcinoma; Microrna; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers, Tumor*
  • Computational Biology / methods
  • Databases, Nucleic Acid
  • Female
  • Gene Expression Profiling
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Reproducibility of Results
  • Squamous Cell Carcinoma of Head and Neck / diagnosis*
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Support Vector Machine

Substances

  • Biomarkers, Tumor
  • MicroRNAs