Prognostic microRNA signatures derived from The Cancer Genome Atlas for head and neck squamous cell carcinomas

Cancer Med. 2016 Jul;5(7):1619-28. doi: 10.1002/cam4.718. Epub 2016 Apr 25.

Abstract

Identification of novel prognostic biomarkers typically requires a large dataset which provides sufficient statistical power for discovery research. To this end, we took advantage of the high-throughput data from The Cancer Genome Atlas (TCGA) to identify a set of prognostic biomarkers in head and neck squamous cell carcinomas (HNSCC) including oropharyngeal squamous cell carcinoma (OPSCC) and other subtypes. In this study, we analyzed miRNA-seq data obtained from TCGA patients to identify prognostic biomarkers for OPSCC. The identified miRNAs were further tested with an independent cohort. miRNA-seq data from TCGA was also analyzed to identify prognostic miRNAs in oral cavity squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC). Our study identified that miR-193b-3p and miR-455-5p were positively associated with survival, and miR-92a-3p and miR-497-5p were negatively associated with survival in OPSCC. A combined expression signature of these four miRNAs was prognostic of overall survival in OPSCC, and more importantly, this signature was validated in an independent OPSCC cohort. Furthermore, we identified four miRNAs each in OSCC and LSCC that were prognostic of survival, and combined signatures were specific for subtypes of HNSCC. A robust 4-miRNA prognostic signature in OPSCC, as well as prognostic signatures in other subtypes of HNSCC, was developed using sequencing data from TCGA as the primary source. This demonstrates the power of using TCGA as a potential resource to develop prognostic tools for improving individualized patient care.

Keywords: Gene signature; The Cancer Genome Atlas; head and neck cancer; microRNA; oropharyngeal cancer; prognosis.

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality*
  • Computational Biology / methods
  • Databases, Nucleic Acid
  • Female
  • Gene Expression Profiling
  • Genomics / methods
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / mortality*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • Prognosis
  • Reproducibility of Results
  • Squamous Cell Carcinoma of Head and Neck
  • Transcriptome*

Substances

  • Biomarkers, Tumor
  • MicroRNAs