Abstract
BackgroundDeregulated miRNAs are found in cancer cells and recently in blood cells of cancer patients. Due to their inherent stability miRNAs may offer themselves for blood based tumor diagnosis. Here we addressed the question whether there is a sufficient number of miRNAs deregulated in blood cells of cancer patients to be able to distinguish between cancer patients and controls.MethodsWe synthesized 866 human miRNAs and miRNA star sequences as annotated in the Sanger miRBase onto a microarray designed by febit biomed gmbh. Using the fully automated Geniom Real Time Analyzer platform, we analyzed the miRNA expression in 17 blood cell samples of patients with non-small cell lung carcinomas (NSCLC) and in 19 blood samples of healthy controls.ResultsUsing t-test, we detected 27 miRNAs significantly deregulated in blood cells of lung cancer patients as compared to the controls. Some of these miRNAs were validated using qRT-PCR. To estimate the value of each deregulated miRNA, we grouped all miRNAs according to their diagnostic information that was measured by Mutual Information. Using a subset of 24 miRNAs, a radial basis function Support Vector Machine allowed for discriminating between blood cellsamples of tumor patients and controls with an accuracy of 95.4% [94.9%-95.9%], a specificity of 98.1% [97.3%-98.8%], and a sensitivity of 92.5% [91.8%-92.5%].ConclusionOur findings support the idea that neoplasia may lead to a deregulation of miRNA expression in blood cells of cancer patients compared to blood cells of healthy individuals. Furthermore, we provide evidence that miRNA patterns can be used to detect human cancers from blood cells.
Highlights
Deregulated miRNAs are found in cancer cells and recently in blood cells of cancer patients
The aim of our study was to address the following questions: Is there a larger number of differentially regulated miRNAs in blood cells of lung cancer patients as compared to healthy controls? To what extend do miRNA expression profiles in blood cells allow for the discrimination of lung cancer patients from controls? What is the information content of single miRNAs for such discrimination? Does the platform used in these experiments offer the option of a highly reproducible and efficient largescale diagnostic test? The answers to these questions will lay the ground for the analysis of blood based miRNA expression profiles in other cancers
Results miRNA experiments We analyzed the expression of 866 miRNAs and miRNA star sequences in blood cells of 17 patients with non-small cell lung carcinomas (NSCLC)
Summary
Deregulated miRNAs are found in cancer cells and recently in blood cells of cancer patients. More than two-thirds of lung cancers are diagnosed at late stages, when the relative survival rate is low [3]. This reality calls for the search of new biomarkers that are able to catch lung cancer while it is still small and locally defined. MicroRNAs (miRNA) are a recently discovered class of small non-coding RNAs (17-24 nucleotides) [4] Due to their function as regulators of gene expression they play a critical role both in physiological and in pathological processes, such as cancer [5,6,7,8]. This fact is outlined by the "Human MiRNAs & Diseases" database, the most comprehensive resource on the web, containing hundreds of entries showing the deregulation of miRNAs in a manifold of human diseases [9]
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