Plasma extracellular vesicle microRNA-491-5p as diagnostic and prognostic marker for head and neck squamous cell carcinoma

Cancer Sci. 2021 Oct;112(10):4257-4269. doi: 10.1111/cas.15067. Epub 2021 Jul 30.


Poor survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is partly due to early diagnosis difficulties and the lack of reliable biomarkers for predicting treatment outcomes. In the discovery cohort, plasma-derived extracellular vesicles (EVs) from LA-HNSCC patients (n = 48) and healthy volunteers (n = 12) were used for profiling for microRNA (miRNA) expression by NanoString analysis. Ten EV-associated miRNAs were differentially expressed between LA-HNSCC patients and healthy volunteers. Subsequently, the results were validated in the individual discovery and additional cases (HNSCC, n = 73; control, n = 20) by quantitative RT-PCR. Among 10 EV-miRNAs, four (miR-27b-3p, miR-491-5p, miR-1910-5p, and miR-630) were significantly dysregulated in LA-HNSCC patients (n = 73) compared with healthy volunteers (n = 20). The miRNA prediction models were developed to discriminate HNSCC patients from healthy volunteers. The model using miR-491-5p was selected as a diagnostic biomarker for LA-HNSCC with a sensitivity and specificity of 46.6% and 100%, respectively (P < .001). The dynamic changes of miRNA model score (ΔmiRNAs) were determined using scores pre- and postdefinitive treatment to further investigate the prognostic value of miRNA prediction models. The univariate and multivariate analyses indicated that ΔmiR-491-5p was the most powerful and independent prognostic indicator for overall survival (hazard ratio [HR] 5.66, 95% confidence interval, 1.77-18.01; P = .003) and disease-free survival (HR 2.82, 95% CI, 1.13-7.05; P = .027) of HNSCC patients. In summary, the miR-491-5p prediction model could serve as a blood-based diagnostic marker for LA-HNSCC. Moreover, ΔmiR-491-5p could be a potential monitoring prognostic marker to reflect the survival of HNSCC patients.

Keywords: biomarker; extracellular vesicle; head and neck squamous cell carcinoma; liquid biopsy; miRNA.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • Confidence Intervals
  • Disease-Free Survival
  • Extracellular Vesicles / genetics*
  • Female
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Humans
  • Male
  • MicroRNAs / blood*
  • Microarray Analysis
  • Middle Aged
  • Prognosis
  • Sensitivity and Specificity
  • Squamous Cell Carcinoma of Head and Neck / blood
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology


  • Biomarkers, Tumor
  • MIRN27 microRNA, human
  • MIRN491 microRNA, human
  • MIRN630 microRNA, human
  • MicroRNAs