Universal disease biomarker: can a fixed set of blood microRNAs diagnose multiple diseases?

BackgroundThe selection of disease biomarkers is often difficult because of their unstable identification, i.e., the selection of biomarkers is heavily dependent upon the set of samples analyzed and the use of independent sets of samples often results in a completely different set of biomarkers being identified. However, if a fixed set of disease biomarkers could be identified for the diagnosis of multiple diseases, the difficulties of biomarker selection could be reduced.ResultsIn this study, the previously identified universal disease biomarker (UDB) consisting of blood miRNAs that could discriminate between patients with multiple diseases and healthy controls was extended to the recently reported independent measurements of blood microRNAs (miRNAs). The performance achieved by UDB in an independent set of samples was competitive with performances achieved with biomarkers selected using lasso, a standard, heavily sample-dependent procedure. Furthermore, the development of stable feature extraction was suggested to be a key factor in constructing more efficient and stable (i.e., sample- and disease-independent) UDBs.ConclusionsThe previously proposed UDB was successfully extended to an additional seven diseases and is expected to be useful for the diagnosis of other diseases.

[1]  T. Poynard,et al.  FibroMAX™: towards a new universal biomarker of liver disease? , 2007, Expert review of molecular diagnostics.

[2]  P. Tan,et al.  Identification of Circulating MicroRNA Signatures for Breast Cancer Detection , 2013, Clinical Cancer Research.

[3]  S. Hébert,et al.  Circulating microRNAs in Alzheimer’s disease: the search for novel biomarkers , 2013, Front. Mol. Neurosci..

[4]  Marcel Scheideler,et al.  Overexpression of primary microRNA 221/222 in acute myeloid leukemia , 2013, BMC Cancer.

[5]  P. Doevendans,et al.  Circulating MicroRNA Profiles for Detection of Peripheral Arterial Disease: Small New Biomarkers for Cardiovascular Disease , 2013, Circulation. Cardiovascular genetics.

[6]  Martial Saugy,et al.  Circulating miRNAs: a new generation of anti-doping biomarkers , 2013, Analytical and Bioanalytical Chemistry.

[7]  Kira S. Sheinerman,et al.  Circulating cell-free microRNA as biomarkers for screening, diagnosis and monitoring of neurodegenerative diseases and other neurologic pathologies , 2013, Front. Cell. Neurosci..

[8]  Yoshiki Murakami,et al.  Principal Component Analysis Based Feature Extraction Approach to Identify Circulating microRNA Biomarkers , 2013, PloS one.

[9]  Gottfried Köhler,et al.  Interleukin 8 (IL-8) - a universal biomarker? , 2010, International archives of medicine.

[10]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[11]  J Waxman,et al.  Circulating microRNAs as potential new biomarkers for prostate cancer , 2013, British Journal of Cancer.

[12]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[13]  S. Ricci,et al.  Conventional and novel diagnostic biomarkers of acute myocardial infarction: a promising role for circulating microRNAs , 2013, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[14]  K. Jellinger,et al.  Biomarkers for early diagnosis of Alzheimer disease: ‘ALZheimer ASsociated gene’– a new blood biomarker? , 2008, Journal of cellular and molecular medicine.

[15]  Sabine C. Mueller,et al.  A blood based 12-miRNA signature of Alzheimer disease patients , 2013, Genome Biology.

[16]  Zoltan Dezso,et al.  Circulating miRNA Biomarkers for Alzheimer's Disease , 2013, Alzheimer's & Dementia.

[17]  Ron Wehrens,et al.  Stability-based biomarker selection. , 2011, Analytica chimica acta.

[18]  O. Slabý,et al.  Circulating miRNAs as new blood-based biomarkers for solid cancers. , 2013, Future oncology.

[19]  C. Woods,et al.  Plasma microRNA signature as a noninvasive biomarker for acute graft-versus-host disease. , 2013, Blood.

[20]  E. Petricoin,et al.  The blood peptidome: a higher dimension of information content for cancer biomarker discovery , 2006, Nature Reviews Cancer.

[21]  P. Doevendans,et al.  Circulating MicroRNAs as Novel Biomarkers for the Early Diagnosis of Acute Coronary Syndrome , 2013, Journal of Cardiovascular Translational Research.

[22]  R. Biondi,et al.  Differential Stability of Cell-Free Circulating microRNAs: Implications for Their Utilization as Biomarkers , 2013, PloS one.

[23]  D. Engelman,et al.  pHLIP and Acidity as a Universal Biomarker for Cancer , 2012, The Yale journal of biology and medicine.

[24]  Christian Langer,et al.  Circulating microRNAs in hematological diseases: principles, challenges, and perspectives. , 2013, Blood.

[25]  A. Krishnamurthy,et al.  Lung cancer detection by screening - presenting circulating miRNAs as a promising next generation biomarker breakthrough. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[26]  Antai Wang,et al.  Exploration of Genome-Wide Circulating MicroRNA in Hepatocellular Carcinoma: MiR-483-5p as a Potential Biomarker , 2013, Cancer Epidemiology, Biomarkers & Prevention.

[27]  Yoshiki Murakami,et al.  Comprehensive miRNA Expression Analysis in Peripheral Blood Can Diagnose Liver Disease , 2012, PloS one.

[28]  C. Garnis,et al.  Differential expression of miRNAs in the serum of patients with high-risk oral lesions , 2012, Cancer medicine.

[29]  Martin Reczko,et al.  DIANA miRPath v.2.0: investigating the combinatorial effect of microRNAs in pathways , 2012, Nucleic Acids Res..

[30]  Sandip Chaugai,et al.  Plasma microRNA-133a is a new marker for both acute myocardial infarction and underlying coronary artery stenosis , 2013, Journal of Translational Medicine.

[31]  S. Hanash,et al.  Emerging molecular biomarkers—blood-based strategies to detect and monitor cancer , 2011, Nature Reviews Clinical Oncology.

[32]  Thomas Tuschl,et al.  Comprehensive profiling of circulating microRNA via small RNA sequencing of cDNA libraries reveals biomarker potential and limitations , 2013, Proceedings of the National Academy of Sciences.