The validity of circulating microRNAs in oncology: Five years of challenges and contradictions

Jarry, Jonathan; Schadendorf, Dirk; Greenwood, Celia M.T.; Spatz, Alan; Kempen, Leon C. van

doi:10.1016/j.molonc.2014.02.009

Cited by 148 publications

(158 citation statements)

References 108 publications

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“…The reproducibility of miR-181a assessments may be affected by: 1) pre-analytical steps such as race, age, and cancer treatments (chemotherapy, surgery, radiation or a combination of these methods) [3, 94]; 2) the handling and technological approach of processing specific samples (mainly serum, plasma) [95, 96]; and 3) methods used for data normalization, i.e. selection of a stable circulating “reference” gene [97, 98].…”

Section: Altered Serum Levels Of Mir-181a As a Diagnostic Biomarkermentioning

confidence: 99%

The Dual Regulatory Role of MiR-181a in Breast Cancer

Yang

Tabatabaei

Ruan

et al. 2017

Cell Physiol Biochem

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MicroRNAs (miRNAs) are a family of highly conserved noncoding single˗stranded RNA molecules of 21 to 25 nucleotides. miRNAs silence their cognate target genes at the post-transcriptional level and have been shown to have important roles in oncogenesis, invasion, and metastasis via epigenetic post-transcriptional gene regulation. Recent evidence indicates that the expression of miR-181a is altered in breast tumor tissue and in the serum of patients with breast cancer. However, there are several contradicting findings that challenge the biological significance of miR-181a in tumor development and metastasis. In fact, some studies have implicated miR-181a in regulating breast cancer gene expression. Here we summarize the current literature demonstrating established links between miR-181a and human breast cancer with a focus on recently identified mechanisms of action. This review also aims to explore the potential of miR-181a as a diagnostic and/or prognostic biomarker for breast cancer and to discuss the contradicting data regarding its targeting therapeutics and the associated challenges.

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Section: Altered Serum Levels Of Mir-181a As a Diagnostic Biomarkermentioning

confidence: 99%

The Dual Regulatory Role of MiR-181a in Breast Cancer

Yang

Tabatabaei

Ruan

et al. 2017

Cell Physiol Biochem

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“…The major difficulty with miRNA assessment is the fact that there are significant inconsistencies in signatures from the same neoplasm [84]. A considerable amount of additional information about miRNA circulatory regulatory mechanisms and their putative biological function is prerequisite to defining their role as a clinically useful biomarker group.…”

Section: Mirnas In Bloodmentioning

confidence: 99%

“…The lack of concordance between circulating and tumor miRNA expression profiles in neoplasia is evident [81, 84, 100, 101]. The correlation between circulating and tumor tissue miRNAs is poor, and substantial investigation is required to elucidate and define the relationship (Fig.…”

Section: Correlating Circulating and Tumor Mirna Expression Profilesmentioning

confidence: 99%

A Comprehensive Assessment of the Role of miRNAs as Biomarkers in Gastroenteropancreatic Neuroendocrine Tumors

et al. 2018

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Background/Aims: A key issue in neuroendocrine neoplasia management is the identification of blood signatures that specifically define the activity of a cancer or local tumor microenvironment. MicroRNAs (miRNAs) may represent such a candidate. To evaluate their clinical utility as biomarkers in gastroenteropancreatic neuroendocrine tumors (GEP-NETs), we assessed their expression in tissue and blood. Methods: A systematic review of PubMed was undertaken to identify studies investigating miRNAs in GEP-NETs and their utility as blood or tissue biomarkers. Results: Twenty-two studies using a range of methodologies with different normalization protocols were identified: tumor – gastric NET type 1 (n = 1 study: MiR-222, regulates p27KIP1), pancreatic (n = 6: MiR-21 [inflammatory marker, oncogene] and MiR-144 [PI₃K/AKT signaling], both up- and downregulated depending on the method), small intestinal (n = 7: no consistent signature), and colorectal (n = 3: no consistent signature); blood – gastric NET type 1 (n = 1: MiR-222), pancreatic (n = 3: MiR-21), and small intestinal (n = 3: no consistent signature). The studies all included heterogeneous cohorts, were insufficiently powered, and utilized different methodologies, and age- and gender-matched controls were not used. Different miRNA isolation methods and detection protocols resulted in inconsistent expression comparing tumor and blood. A scientific discrepancy was the downregulated expression of some circulating candidates compared to tissue levels, suggesting methodological issues or physiological responses to the tumor. Both are of concern in defining the biometrics of a marker. Conclusions: A potential biomarker for GEP-NETs included MiR-21 (small bowel and pancreas), but this epithelial tumor marker requires prospective validation. Overall, significant scientific investigation remains to identify and demonstrate neuroendocrine specificity and to validate candidate miRNA biomarkers.

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“…Due to the inherent assumption that circulating miRNAs are altered in a specific manner for a particular disease, it is beneficial to correlate with tissue concentrations. One recent review reported that only 49% of published circulating miRNA signatures in cancer have an accompanying study of miRNA expression in corresponding tissue and only 7% show perfect correlation in a discovery setting [4]. The challenge of matching circulating and tissue miRNAs is highlighted by a recent comparison of tissue and plasma miRNAs in pancreatic adenocarcinoma that noted concordant overexpression of only two of eight studied miRNAs [49].…”

Section: Pre-analytical Variables For Circulating Mirnasmentioning

confidence: 99%

“…However, studies to date have yielded inconsistent results and clinical assays remain elusive. A number of recent reviews [1][2][3][4][5][6][7][8][9] have thoroughly discussed the challenges and pitfalls involved in accurately quantifying miRNAs, including pre-analytical, analytical, and methodological factors that contribute to result heterogeneity. There is clearly an urgent need for a global consensus on study design and laboratory procedures.…”

Section: Introductionmentioning

confidence: 99%

Variability in, variability out: best practice recommendations to standardize pre-analytical variables in the detection of circulating and tissue microRNAs

Khan

Lieberman

Lockwood

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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microRNAs (miRNAs) hold promise as biomarkers for a variety of disease processes and for determining cell differentiation. These short RNA species are robust, survive harsh treatment and storage conditions and may be extracted from blood and tissue. Pre-analytical variables are critical confounders in the analysis of miRNAs: we elucidate these and identify best practices for minimizing sample variation in blood and tissue specimens. Preanalytical variables addressed include patient-intrinsic variation, time and temperature from sample collection to storage or processing, processing methods, contamination by cells and blood components, RNA extraction method, normalization, and storage time/conditions. For circulating miRNAs, hemolysis and blood cell contamination significantly affect profiles; samples should be processed within 2 h of collection; ethylene diamine tetraacetic acid (EDTA) is preferred while heparin should be avoided; samples should be "double spun" or filtered; room temperature or 4 °C storage for up to 24 h is preferred; miRNAs are stable for at least 1 year at -20 °C or -80 °C. For tissuebased analysis, warm ischemic time should be < 1 h; cold ischemic time (4 °C) < 24 h; common fixative used for all specimens; formalin fix up to 72 h prior to processing; enrich for cells of interest; validate candidate biomarkers with in situ visualization. Most importantly, all specimen types should have standard and common workflows with careful documentation of relevant pre-analytical variables.

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The validity of circulating microRNAs in oncology: Five years of challenges and contradictions

Cited by 148 publications

References 108 publications

The Dual Regulatory Role of MiR-181a in Breast Cancer

The Dual Regulatory Role of MiR-181a in Breast Cancer

A Comprehensive Assessment of the Role of miRNAs as Biomarkers in Gastroenteropancreatic Neuroendocrine Tumors

Variability in, variability out: best practice recommendations to standardize pre-analytical variables in the detection of circulating and tissue microRNAs

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