A microRNA-based prediction algorithm for diagnosis of non-small lung cell carcinoma in minimal biopsy material

N G Bediaga, M P A Davies, A Acha-Sagredo, R Hyde, O Y Raji, R Page, M Walshaw, J Gosney, A Alfirevic, J K Field, T Liloglou

Research output: Contribution to journalArticle (journal)peer-review

21 Citations (Scopus)


BACKGROUND: Diagnosis is jeopardised when limited biopsy material is available or histological quality compromised. Here we developed and validated a prediction algorithm based on microRNA (miRNA) expression that can assist clinical diagnosis of lung cancer in minimal biopsy material to improve clinical management.

METHODS: Discovery utilised Taqman Low Density Arrays (754 miRNAs) in 20 non-small cell lung cancer (NSCLC) tumour/normal pairs. In an independent set of 40 NSCLC patients, 28 miRNA targets were validated using qRT-PCR. A prediction algorithm based on eight miRNA targets was validated blindly in a third independent set of 47 NSCLC patients. The panel was also tested in formalin-fixed paraffin-embedded (FFPE) specimens from 20 NSCLC patients. The genomic methylation status of highly deregulated miRNAs was investigated by pyrosequencing.

RESULTS: In the final, frozen validation set the panel had very high sensitivity (97.5%), specificity (96.3%) and ROC-AUC (0.99, P=10(-15)). The panel provided 100% sensitivity and 95% specificity in FFPE tissue (ROC-AUC=0.97 (P=10(-6))). DNA methylation abnormalities contribute little to the deregulation of the miRNAs tested.

CONCLUSION: The developed prediction algorithm is a valuable potential biomarker for assisting lung cancer diagnosis in minimal biopsy material. A prospective validation is required to measure the enhancement of diagnostic accuracy of our current clinical practice.

Original languageEnglish
Pages (from-to)2404-11
Number of pages8
JournalBritish Journal of Cancer
Issue number9
Publication statusPublished - 29 Oct 2013


  • Aged
  • Algorithms
  • Biomarkers, Tumor/genetics
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung/diagnosis
  • DNA Methylation
  • Female
  • Gene Expression
  • Humans
  • Lung Neoplasms/diagnosis
  • Male
  • MicroRNAs/genetics
  • Models, Biological
  • Models, Statistical
  • Paraffin Embedding


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