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

Hennessey, PT and Sanford, T and Choudhary, A and Mydlarz, WW and Brown, D and Adai, AT and Ochs, MF and Ahrendt, SA and Mambo, E and Califano, JA (2012) Serum microrna biomarkers for detection of non-small cell lung cancer. PLoS ONE, 7 (2).

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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. © 2012 Hennessey et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Hennessey, PT
Sanford, T
Choudhary, A
Mydlarz, WW
Brown, D
Adai, AT
Ochs, MF
Ahrendt, SAsaa39@pitt.eduSAA39
Mambo, E
Califano, JA
ContributionContributors NameEmailPitt UsernameORCID
Date: 28 February 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0032307
Refereed: Yes
MeSH Headings: Adult; Aged; Carcinoma, Non-Small-Cell Lung--blood; Carcinoma, Non-Small-Cell Lung--diagnosis; Female; Humans; Lung Neoplasms--blood; Lung Neoplasms--diagnosis; Male; MicroRNAs--blood; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; Tumor Markers, Biological--blood
Other ID: NLM PMC3289652
PubMed Central ID: PMC3289652
PubMed ID: 22389695
Date Deposited: 13 Sep 2012 18:06
Last Modified: 19 Jan 2019 14:55


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