Serum microrna biomarkers for detection of non-small cell lung cancer

Patrick T. Hennessey, Tiffany Sanford, Ashish Choudhary, Wojciech Mydlarz, David Brown, Alex Tamas Adai, Michael F. Ochs, Steven A. Ahrendt, Elizabeth Mambo, Joseph A. Califano

Research output: Contribution to journalArticle

Abstract

Non small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality world-wide and the majority of cases are diagnosed at late stages of disease. There is currently no cost-effective screening test for NSCLC, and the development of such a test is a public health imperative. Recent studies have suggested that chest computed tomography screening of patients at high risk of lung cancer can increase survival from disease, however, the cost effectiveness of such screening has not been established. In this Phase I/II biomarker study we examined the feasibility of using serum miRNA as biomarkers of NSCLC using RT-qPCR to examine the expression of 180 miRNAs in sera from 30 treatment naive NSCLC patients and 20 healthy controls. Receiver operating characteristic curves (ROC) and area under the curve were used to identify differentially expressed miRNA pairs that could distinguish NSCLC from healthy controls. Selected miRNA candidates were further validated in sera from an additional 55 NSCLC patients and 75 healthy controls. Examination of miRNA expression levels in serum from a multi-institutional cohort of 50 subjects (30 NSCLC patients and 20 healthy controls) identified differentially expressed miRNAs. A combination of two differentially expressed miRNAs miR-15b and miR-27b, was able to discriminate NSCLC from healthy controls with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100% in the training set. Upon further testing on additional 130 subjects (55 NSCLC and 75 healthy controls), this miRNA pair predicted NSCLC with a specificity of 84% (95% CI 0.73-0.91), sensitivity of 100% (95% CI; 0.93-1.0), NPV of 100%, and PPV of 82%. These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of NSCLC. Further testing in a Phase III biomarker study in is necessary for validation of these results.

Original languageEnglish (US)
Article numbere32307
JournalPLoS One
Volume7
Issue number2
DOIs
StatePublished - Feb 28 2012

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Biomarkers
lung neoplasms
MicroRNAs
microRNA
Non-Small Cell Lung Carcinoma
biomarkers
Cells
Serum
cells
Screening
screening
Testing
Public health
Costs and Cost Analysis
Cost effectiveness
Cost of Illness
Tomography
Feasibility Studies
Costs
testing

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hennessey, P. T., Sanford, T., Choudhary, A., Mydlarz, W., Brown, D., Adai, A. T., ... Califano, J. A. (2012). Serum microrna biomarkers for detection of non-small cell lung cancer. PLoS One, 7(2), [e32307]. https://doi.org/10.1371/journal.pone.0032307

Serum microrna biomarkers for detection of non-small cell lung cancer. / Hennessey, Patrick T.; Sanford, Tiffany; Choudhary, Ashish; Mydlarz, Wojciech; Brown, David; Adai, Alex Tamas; Ochs, Michael F.; Ahrendt, Steven A.; Mambo, Elizabeth; Califano, Joseph A.

In: PLoS One, Vol. 7, No. 2, e32307, 28.02.2012.

Research output: Contribution to journalArticle

Hennessey, PT, Sanford, T, Choudhary, A, Mydlarz, W, Brown, D, Adai, AT, Ochs, MF, Ahrendt, SA, Mambo, E & Califano, JA 2012, 'Serum microrna biomarkers for detection of non-small cell lung cancer', PLoS One, vol. 7, no. 2, e32307. https://doi.org/10.1371/journal.pone.0032307
Hennessey PT, Sanford T, Choudhary A, Mydlarz W, Brown D, Adai AT et al. Serum microrna biomarkers for detection of non-small cell lung cancer. PLoS One. 2012 Feb 28;7(2). e32307. https://doi.org/10.1371/journal.pone.0032307
Hennessey, Patrick T. ; Sanford, Tiffany ; Choudhary, Ashish ; Mydlarz, Wojciech ; Brown, David ; Adai, Alex Tamas ; Ochs, Michael F. ; Ahrendt, Steven A. ; Mambo, Elizabeth ; Califano, Joseph A. / Serum microrna biomarkers for detection of non-small cell lung cancer. In: PLoS One. 2012 ; Vol. 7, No. 2.
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