title: Global analysis of serum microRNAs as potential biomarkers for lung adenocarcinoma.
abstract: Early diagnosis and the ability to predict the most relevant treatment option for individuals is essential to improve clinical outcomes for non-small cell lung cancer (NSCLC) patients. Adenocarcinoma (ADC), a subtype of NSCLC, is the single biggest cancer killer and therefore an urgent need to identify minimally invasive biomarkers to enable early diagnosis. Recent studies, by ourselves and others, indicate that circulating miRNAs have potential as biomarkers. Here we applied global profiling approaches in serum from patients with ADC of the lung to explore if miRNAs have potential as diagnostic biomarkers. This study involved RNA isolation from 80 sera specimens including those from ADC patients (equal numbers of stages 1, 2, 3, and 4) and age- and gender-matched controls (n = 40 each). Six hundred and sixty-seven miRNAs were co-analyzed in these specimens using TaqMan low density arrays and qPCR validation using individual miRNAs. Overall, approximately 390 and 370 miRNAs were detected in ADC and control sera, respectively. A group of 6 miRNAs, miR-30c-1* (AUC = 0.74; P<0.002), miR-616* (AUC = 0.71; P = 0.001), miR-146b-3p (AUC = 0.82; P<0.0001), miR-566 (AUC = 0.80; P<0.0001), miR-550 (AUC = 0.72; P = 0.0006), and miR-939 (AUC = 0.82; P<0.0001) was found to be present at substantially higher levels in ADC compared with control sera. Conversely, miR-339-5p and miR-656 were detected at substantially lower levels in ADC sera (co-analysis resulting in AUC = 0.6; P = 0.02). Differences in miRNA profile identified support circulating miRNAs having potential as diagnostic biomarkers for ADC. More extensive studies of ADC and control serum specimens are warranted to independently validate the potential clinical relevance of these miRNAs as minimally invasive biomarkers for ADC.
authors.affiliation: School of Pharmacy & Pharmaceutical Sciences and Trinity Biomedical Sciences Institute; Trinity College Dublin; Dublin, Ireland.
authors.forename: Sweta
authors.initials: S
authors.lastname: Rani
authors.affiliation: Institute of Molecular Medicine; Trinity Centre for Health Sciences; St. James's Hospital; Trinity College Dublin; Dublin, Ireland.
authors.forename: Kathy
authors.initials: K
authors.lastname: Gately
authors.affiliation: Molecular Therapeutics for Cancer Ireland (MTCI) & St. Vincent's University Hospital; Dublin, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Crown
authors.affiliation: Institute of Molecular Medicine; Trinity Centre for Health Sciences; St. James's Hospital; Trinity College Dublin; Dublin, Ireland.
authors.forename: Ken
authors.initials: K
authors.lastname: O'Byrne
authors.affiliation: School of Pharmacy & Pharmaceutical Sciences and Trinity Biomedical Sciences Institute; Trinity College Dublin; Dublin, Ireland.
authors.forename: Lorraine
authors.initials: L
authors.lastname: O'Driscoll
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: ROC curve; adenocarcinoma; biomarker; circulating; lung cancer; micro-RNAs (miRNAs); minimally invasive
references.citation: Nat Cell Biol. 2008 Dec;10(12):1470-6
references.pmid: 19011622
references.citation: Gene. 2012 Sep 15;506(2):355-9
references.pmid: 22732573
references.citation: Cancer Genomics Proteomics. 2008 Mar-Apr;5(2):94-104
references.pmid: 18460738
references.citation: Int J Cancer. 2012 Apr 1;130(7):1620-8
references.pmid: 21557218
references.citation: Biochem Biophys Res Commun. 2011 Mar 4;406(1):70-3
references.pmid: 21295551
references.citation: Eur J Cancer. 2011 Mar;47(5):784-91
references.pmid: 21112772
references.citation: Mol Oncol. 2011 Jun;5(3):281-91
references.pmid: 21398193
references.citation: N Engl J Med. 2011 Mar 10;364(10):947-55
references.pmid: 21388312
references.citation: Urology. 2011 May;77(5):1265.e9-16
references.pmid: 21539977
references.citation: J Thorac Oncol. 2011 Mar;6(3):482-8
references.pmid: 21258252
references.citation: Eur Respir J. 2011 Mar;37(3):617-23
references.pmid: 20595154
references.citation: J Clin Oncol. 2010 Apr 1;28(10):1721-6
references.pmid: 20194856
references.citation: BMC Cancer. 2011 Aug 24;11:374
references.pmid: 21864403
references.citation: Lab Invest. 2011 Apr;91(4):579-87
references.pmid: 21116241
references.citation: PLoS One. 2010 Oct 29;5(10):e13735
references.pmid: 21060830
references.citation: Clin Cancer Res. 2010 Jan 15;16(2):430-41
references.pmid: 20068076
references.citation: J Cell Physiol. 2005 Apr;203(1):1-5
references.pmid: 15389637
references.citation: PLoS One. 2012;7(2):e32307
references.pmid: 22389695
references.citation: Int J Cancer. 2012 Mar 15;130(6):1378-86
references.pmid: 21544802
references.citation: Lung Cancer. 2012 May;76(2):191-6
references.pmid: 22115706
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3713-8
references.pmid: 21300873
references.citation: Cancer Res. 2010 Jan 1;70(1):36-45
references.pmid: 20028859
references.citation: J Clin Gastroenterol. 2011 Apr;45(4):355-60
references.pmid: 21278583
references.citation: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references.pmid: 20610543
references.citation: PLoS One. 2012;7(5):e36530
references.pmid: 22590557
references.citation: Cancer Res. 2009 Jul 15;69(14):5776-83
references.pmid: 19584273
references.citation: Ann Surg. 2013 Mar;257(3):548-54
references.pmid: 23011390
references.citation: Cell Res. 2008 Oct;18(10):997-1006
references.pmid: 18766170
references.citation: Clin Lung Cancer. 2009 Jan;10(1):42-6
references.pmid: 19289371
references.citation: Carcinogenesis. 2012 May;33(5):1046-54
references.pmid: 22331473
references.citation: Bioinformatics. 2009 Aug 1;25(15):1991-3
references.pmid: 19435746
references.citation: J Clin Oncol. 2010 Dec 20;28(36):5311-20
references.pmid: 21079145
references.citation: J Thorac Oncol. 2010 Feb;5(2):153-7
references.pmid: 20101143
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8
references.pmid: 18663219
references.citation: Breast Cancer Res Treat. 2010 Oct;123(3):613-25
references.pmid: 20549336
references.citation: Arch Pathol Lab Med. 2011 Jan;135(1):110-6
references.pmid: 21204716