High-throughput qRT-PCR validation of blood microRNAs in non-small cell lung cancer

Leidinger, Petra; Brefort, Thomas; Backes, Christina; Krapp, Medea; Galata, Valentina; Beier, Markus; Kohlhaas, Jochen; Huwer, Hanno; Meese, Eckart; Keller, Andreas

doi:10.18632/oncotarget.6566

Cited by 68 publications

(62 citation statements)

References 22 publications

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“…The study on Alzheimer's disease included, for example, 103 patients with Alzheimer's disease, 77 unaffected controls, and 110 disease controls (e.g., mild cognitive impairment). For lung cancer patients, we successfully validated a signature that was originally generated by microarrays [68] by using high-throughput RT-qPCR [72]. However, there are also reports of failed attempts to reproduce miRNA signatures.…”

Section: Mirna Signaturesmentioning

confidence: 99%

Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects

2016

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Significant effort has been devoted to discovering microRNA (miRNA) disease biomarkers. In particular, miRNAs in whole blood or specific blood components are candidates for improving the diagnosis of diseases, including life-threatening pathologies. This review covers the challenges crucial for the translation of miRNAs in body fluids (circulating miRNAs) from a research setting into a clinical care scenario. First, we discuss the specificity of miRNA biomarkers for the diagnosis of a disease. While single miRNAs such as miR-20a, miR-21, miR-155, and miR-126 are frequently not disease specific, miRNA signatures that consist of a plurality of different miRNAs may help to improve differentiation between pathologies. Second, we discuss the degree of reproducibility and highlight selected validation studies. While single miRNA markers are often confirmed by independent studies, miRNA signatures are less frequently verified. Third, we address challenges to the profiling of miRNAs in high-throughput settings and we discuss the appropriateness of various analytical platforms and bioinformatics towards a clinical application of miRNAs. Finally, we shed light on the suitability of enriched miRNA sources, e.g. fractionation of body fluids for extracellular vesicles such as exosomes or blood cells, to develop miRNA signatures. With an increasing number of verified miRNA signatures and with the advance of matured medium-throughput approaches in clinical settings, specific miRNA markers are increasingly likely to contribute to human healthcare.

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Section: Mirna Signaturesmentioning

confidence: 99%

Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects

2016

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“…In an exploratory phase I/II biomarker study, Hennessey et al identified a miRNA pair (miRNA-15b and miRNA-27b) able to distinguish between NSCLC (n 5 55) and cancer-free patients (n 5 75), with a specificity of 84% (95% CI, 0.73-0.91) and sensitivity of 100% (95% CI,0.93-1.0) [42]. Leidinger et al used qRT-PCR analysis to identify a set of five markers able to separate lung cancer patients (n 5 74) from healthy controls (n 5 20), with a specificity of 98% (95% CI, 0.95-1.0) and sensitivity of 91% (95% CI, 0.87-0.94) [43]. In addition, they were able to differentiate NSCLC patients (n 5 74) from patients with chronic obstructive pulmonary disease (n 5 26), with a specificity of 81% and sensitivity of 86% using 10 miRNA markers.…”

Section: Diagnosis and Screening Of Lung Cancermentioning

confidence: 99%

Clinical Utility of Liquid Diagnostic Platforms in Non-Small Cell Lung Cancer

Levy

Cordova

et al. 2016

The Oncologist

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A firmer understanding of the genomic landscape of lung cancer has recently led to targeted, therapeutic advances in non-small cell lung cancer. Historically, the reference standard for the diagnosis and genetic interrogation for advanced-stage patients has been tissue acquisition via computed tomography-guided core or fine needle aspiration biopsy. However, this process can frequently put the patient at risk and remains complicated by sample availability and tumor heterogeneity. In addition, the time required to complete the diagnostic assays can negatively affect clinical care. Technological advances in recent years have led to the development of blood-based diagnostics or “liquid biopsies” with great potential to quickly diagnose and genotype lung cancer using a minimally invasive technique. Recent studies have suggested that molecular alterations identified in cell-free DNA (cfDNA) or circulating tumor DNA can serve as an accurate molecular proxy of tumor biology and reliably predict the response to tyrosine kinase therapy. In addition, several trials have demonstrated the high accuracy of microRNA (miRNA) platforms in discerning cancerous versus benign nodules in high-risk, screened patients. Despite the promise of these platforms, issues remain, including varying sensitivities and specificities between competing platforms and a lack of standardization of techniques and downstream processing. In the present report, the clinical applications of liquid biopsy technologies, including circulating tumor cells, proteomics, miRNA, and cfDNA for NSCLC, are reviewed and insight is provided into the diagnostic and therapeutic implications and challenges of these platforms.

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“…The data of miRNA profiles in different conditions in this study rely on Agilent's microarray technology, which has shown a high reproducibility and acceptable sensitivity in previous studies. 5 Using microarrays we recently published a Human miRNA Tissue Atlas, which is freely accessible (www.ccb.uni-saarland.de/tissueatlas). 6 In this study we first investigated the influence of degradation on tissue miRNA patterns and then profiled altogether 31 different organs from 2 corpses.…”

Section: Introductionmentioning

confidence: 99%

Distribution of microRNA biomarker candidates in solid tissues and body fluids

et al. 2016

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Small non-coding RNAs, especially microRNAs, are discussed as promising biomarkers for a substantial number of human pathologies. A broad understanding in which solid tissues, cell types or body fluids a microRNA is expressed helps also to understand and to improve the suitability of miRNAs as non-or minimally-invasive disease markers. We recently reported the Human miRNA Tissue Atlas (http://www.ccb.uni-saarland.de/tissueatlas) containing 105 miRNA profiles of 31 organs from 2 corpses. We subsequently added miRNA profiles measured by others and us using the same array technology as for the first version of the Human miRNA Tissue Atlas. The latter profiles stem from 163 solid organs including lung, prostate and gastric tissue, from 253 whole blood samples and 66 fractioned blood cell isolates, from body fluids including 72 serum samples, 278 plasma samples, 29 urine samples, and 16 saliva samples and from different collection and storage conditions. While most miRNAs are ubiquitous abundant in solid tissues and whole blood, we also identified miRNAs that are rather specific for tissues. Our web-based repository now hosting 982 full miRNomes all of which are measured by the same microarray technology. The knowledge of these variant abundances of miRNAs in solid tissues, in whole blood and in other body fluids is essential to judge the value of miRNAs as biomarker.

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High-throughput qRT-PCR validation of blood microRNAs in non-small cell lung cancer

Cited by 68 publications

References 22 publications

Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects

Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects

Clinical Utility of Liquid Diagnostic Platforms in Non-Small Cell Lung Cancer

Distribution of microRNA biomarker candidates in solid tissues and body fluids

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