miRNAs in lung cancer - Studying complex fingerprints in patient's blood cells by microarray experiments

Keller, Andreas; Leidinger, Petra; Borries, Anne; Wendschlag, Anke; Wucherpfennig, Frank; Scheffler, Matthias; Huwer, Hanno; Lenhof, Hans‐Peter; Meese, Eckart

doi:10.1186/1471-2407-9-353

Cited by 132 publications

(126 citation statements)

References 42 publications

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“…Since the proportion of circulating miRNAs of the total miRNAs in blood samples is small, variations are mainly caused by the blood cells and may be the result of systemic reactions linked to the tumour disease. In conclusion, a tumour characteristic miRNA pattern results from a specific reaction of the organism (24,25).…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNAs in blood and urine as tumour markers for the detection of urinary bladder cancer

et al. 2013

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Abstract. Since differential expression of microRNAs (miRNAs) has been found to be highly associated with several types of cancer, the goal of the present study was to identify an miRNA fingerprint as a non-invasive diagnostic tool to detect urinary bladder cancer using the easily accessible samples of whole blood and urine. Blood and urine samples from 4 controls and from patients suffering from superficial and invasive bladder cancer were analyzed using miRNA microarray consisting of 754 human miRNAs from the Sanger database v14. Using RT-qPCR technique, 6 of the differentially expressed miRNAs were validated in the controls (20 blood, 19 urine samples) and patients with superficial (18 blood, 16 urine samples) or invasive (20 blood and urine samples each) tumours. Three blood miRNAs (miR-26b-5p, miR-144-5p, miR-374-5p) were found to be significantly upregulated in invasive bladder tumour patients (P<0.05) when compared to the control group. The expression of 2 miRNAs (miR-618, miR-1255b-5p) in the urine of patients with invasive tumours was significantly (P<0.05) increased in comparison to the control group. Blood miR-26b-5p detected the presence of invasive bladder tumours with 94% specificity and 65% sensitivity. The urine miR-1255b-5p reached 68% specificity and 85% sensitivity in the diagnosis of invasive tumours. This pilot study represents the first characterization of an miRNA profile for urinary bladder tumours in whole blood samples. In addition, it was shown that invasive bladder tumours could be identified by differentially expressed urine miRNAs. Further studies are needed to test the clinical usefulness for bladder cancer detection and surveillance.

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Section: Discussionmentioning

confidence: 99%

Identification of microRNAs in blood and urine as tumour markers for the detection of urinary bladder cancer

et al. 2013

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“…These molecules, which act as post-transcriptional gene expression silencers, possess a well-known role in lung development, and their aberrant expression may drive the onset of lung cancer (Wu et al, 2009). The different miRNA profiles between normal lung and lung cancer suggest for these molecules the role of reliable biomarkers and their potential use as diagnostic and prognostic tools in lung cancer (Tong, 2006;Yanaihara et al, 2006;Keller et al, 2009;Lodes et al, 2009;Wang et al, 2009;Xie et al, 2010). Moreover, miRNA molecules are extremely stable in tissues and in biological fluids, where they are present due to cell lysis or to active exocytosis processes (Simpson et al, 2009).…”

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confidence: 99%

Reducing the risk of overdiagnosis in lung cancer: A support from molecular biology

Barba¹,

Felsani

Rinaldi³

et al. 2011

Journal Cellular Physiology

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Early detection and swift treatment, when achievable, may significantly affect prognosis in lung cancer patients. Therefore, individuals with a high risk for lung cancer are invited to participate into international screening programs, such as the International Early Lung Cancer Action Program (I-ELCAP). An undesirable consequence of such massive enterprises is the detection of pulmonary nodules also in subjects who are unlikely to ultimately die from lung cancer. Nevertheless, the individuals with pulmonary nodule undergo stringent diagnostic procedures to assess the nature of the lesion. This implies a noticeable (physical and emotional) stress for our patients and the likelihood of overdiagnosis and, potentially, consequent overtreatment. Molecular markers, more specifically, microRNAs, might significantly add value to the workup process aiming at the distinction between benign and malignant lesions and, among the malignant ones, those concretely threatening for the patients' survival. We are confident that such a multidisciplinary approach would better suit our patients' diagnostic and/or therapeutic, actual needs.J. Cell. Physiol. 226: 2213-2214, 2011. ß 2010 Wiley-Liss, Inc.Lung cancer represents the leading cause of cancer death in Western countries (Herbst et al., 2008;Jemal et al., 2009). Currently, less than 20% of lung cancer patients are diagnosed with a locally confined disease, while locally advanced and disseminated lung cancer still account for the greatest majority of incident cases. As a result, the 5-year survival for all stages combined is 15% (Jemal et al., 2009 A relevant criticism has been addressed to the I-ELCAP study methodology and, in general, to the risk of overdiagnosis (and often overtreatment) which can arise in this kind of massive screenings (Bach et al., 2007;Welch et al., 2007;Bach, 2008b;Reich, 2008;Toyoda et al., 2008;Welch and Black, 2010). This screening generated a remarkable body of evidence on the morphologic features of pulmonary lesions of indeterminate origin, being one single, non-calcified lung nodule detectable in as much as 20% of the screened participants . Essentially, for the optimal management of the patient with LDCT-detected pulmonary nodules, the key questions are: (a) whether these pulmonary lesions would be benign or malignant; (b) if malignant, at what extent they would be life-threatening for the patient; and, consequently, (c) if specific determinations could address the patient toward a definite therapeutic protocol. This emerges as increasingly important in the light of novel natural history models prospected for lung cancer (Bach, 2008a). Thus far, the achievement of a definitive diagnosis of lung cancer appears difficult and challenging, when issued from the sole imaging parameters. Thus, once positive to the screening, patients undergo a stringent, complex and often risky diagnostic schedule. These procedures can imply further, and sometimes repetitive, dangerous radiation exposure for medical imaging (Fazel et al., 2009;Marshall, 2010)

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“…miRNAs and mRNAs are present in all body fluids (Kosaka et al 2010b;El-Hefnawy et al 2004;Bianchi, Maron, and Johnson 2010;Li et al 2004b;Weber et al 2010). Although miRNA and mRNA profiles from whole blood have been published (Hausler et al 2010;Tan et al 2009;Keller et al 2009;Li et al 2004a;Wong et al 2008), circulating RNAs in whole blood samples are impacted by the ratio of cells contained in the whole blood and by the time of storage of the whole blood. For example, miRNAs let-7b, miR-16, miR-7, and miR-145 are differentially expressed by platelets in response to storage at room temperature (Zimmerman and Weyrich 2008;Kannan et al 2009).…”

Section: Sample Collection Processing and Analysis Methodsmentioning

confidence: 99%

Frontiers in Preclinical Safety Biomarkers

et al. 2012

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The measurement of plasma microRNAs (miRNAs) and messenger RNAs (mRNAs) is the most recent effort to identify novel biomarkers in preclinical safety. These genomic markers often display tissue-specific expression, may be released from the tissues into the plasma during toxic events, change early and with high magnitude in tissues and in the blood during specific organ toxicities, and can be measured using multiplex formats. Their validation as biomarkers has been challenged by the technical difficulties. In particular, the concentration of miRNAs in the plasma depends on contamination by miRNAs originating from blood cells and platelets, and the relative fraction of miRNAs in complexes with Argonaute 2, high-density lipoproteins, and in exosomes and microvesicles. In spite of these hurdles, considerable progress has recently been made in assessing the potential value of miRNAs in the clinic, especially in cancer patients and cardiovascular diseases. The future of miRNAs and mRNAs as biomarkers of disease and organ toxicity depends on our ability to characterize their kinetics and to establish robust collection and measurement methods. This review covers the basic biology of miRNAs and the published literature on the use of miRNAs and mRNAs as biomarkers of specific target organ toxicity.

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miRNAs in lung cancer - Studying complex fingerprints in patient's blood cells by microarray experiments

Cited by 132 publications

References 42 publications

Identification of microRNAs in blood and urine as tumour markers for the detection of urinary bladder cancer

Identification of microRNAs in blood and urine as tumour markers for the detection of urinary bladder cancer

Reducing the risk of overdiagnosis in lung cancer: A support from molecular biology

Frontiers in Preclinical Safety Biomarkers

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