Plasma Components Affect Accuracy of Circulating Cancer-Related MicroRNA Quantitation

Kim, Dong Ja; Linnstaedt, Sarah D.; Palma, Jaime; Park, Joon Cheol; Ntrivalas, Evangelos; Kwak‐Kim, Joanne; Gilman‐Sachs, Alice; Beaman, Kenneth D.; Hastings, Michelle L.; Martin, Jeffrey N.; Duelli, Dominik M.

doi:10.1016/j.jmoldx.2011.09.002

Cited by 157 publications

(163 citation statements)

References 56 publications

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“…Also, the different kind of anticoagulants used can influence the results. Thus, Kim et al [26] observed that the levels of miR-16 and miR-223 are lower when heparin is used and higher with oxalate, while EDTA provides similar results to serum. Hemolysis is also a factor that affects the analysis of some miRNAs, including miR-16, miR-451, miR-92a and miR-486-5p that are released by erythrocytes [27,28].…”

Section: Preanalytical and Analytical Variables In Mirna Measurementmentioning

confidence: 99%

miRNAs as novel biomarkers in the management of prostate cancer

Filella

Foj

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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microRNAs (miRNAs) are small non-coding RNAs that control gene expression posttranscriptionally and are part of the giant non codifying genoma. Cumulating data suggest that miRNAs are promising potential biomarkers for many diseases, including cancer. Prostate cancer (PCa) detection is currently based in the serum prostate-specific antigen biomarker and digital rectal examination. However, these methods are limited by a low predictive value and the adverse consequences associated with overdiagnosis and overtreatment. New biomarkers that could be used for PCa detection and prognosis are still needed. Recent studies have demonstrated that aberrant expressions of microRNAs are associated with the underlying mechanisms of PCa. This review attempts to extensively summarize the current knowledge of miRNA expression patterns, as well as their targets and involvement in PCa pathogenesis. We focused our review in the value of circulating and urine miRNAs as biomarkers in PCa patients, highlighting the existing discrepancies between different studies, probably associated with the important methodological issues related to their quantitation and normalization. The majority of studies have been performed in serum or plasma, but urine obtained after prostate massage appears as a new way to explore the usefulness of miRNAs. Large screening studies to select a miRNA profile have been completed, but bioinformatics tools appear as a new approach to select miRNAs that are relevant in PCa development.Promising preliminary results were published concerning miR-141, miR-375 and miR-21, but larger and prospective studies using standardized methodology are necessary to define the value of miRNAs in the detection and prognosis of PCa.

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Section: Preanalytical and Analytical Variables In Mirna Measurementmentioning

confidence: 99%

miRNAs as novel biomarkers in the management of prostate cancer

Filella

Foj

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…For additional profiling of unfractionated plasma or serum, the foremost concerns are to establish standardized sampling and processing protocols (43)(44)(45)(46); account for the effects of RNA extraction methods (9,47,48 ), profiling platforms (49,50 ), and analysis (46 ); and develop and adhere to norms for reporting of methods and data (12,(51)(52)(53)(54). These issues have been addressed adequately elsewhere and also apply to other biofluids and more-focused studies on EVs.…”

Section: Profiling Of Unfractionated Plasma or Serummentioning

confidence: 99%

Circulating MicroRNA Biomarker Studies: Pitfalls and Potential Solutions

2015

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BACKGROUND Circulating microRNAs have been proposed as disease biomarkers that may aid in risk assessment, diagnosis, prognosis, and monitoring of treatment response. The perceived opportunity has loomed particularly large in neoplastic disease, where alterations in cancer cells are thought to be reflected in the extracellular space as affected cells release upregulated miRNAs or fail to release apparently downregulated species. Despite the promise of miRNA biomarkers, evaluation of the diagnostic specificity and reproducibility of reported markers suggests that realizing this promise remains a work in progress. CONTENTS This review examines issues of diagnostic specificity and reproducibility that have afflicted circulating miRNA studies. Surveying the breast cancer literature as an example, few miRNAs are reported consistently. Furthermore, it is posited that the assumptions underlying models of direct contributions of diseased tissue to biofluid miRNA profiles may not hold. Suggestions for improving diagnostic specificity and reliability are provided. SUMMARY To maximize the likelihood of return on investment as miRNAs continue to be evaluated as specific and clinically useful markers, a focus is needed on miRNAs found in specific carriers, such as extracellular vesicles. Alternative sampling techniques should be developed, and nonblood biofluids should be considered. Careful optimization and standardization of preanalytical and analytical methods is needed to ensure that future results, positive or negative, are reliable.

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“…Heparin is commonly used as an anticoagulant in cardiovascular diagnostics and interventions. Previous studies have demonstrated that heparin can inhibit RNA quantification in vitro by interfering with the DNA polymerase used in the quantitative PCR (qPCR) reaction (3 ). It is unclear, however, whether the biologically active concentrations of heparin achieved after treatment of patients influences the quantification of miRNAs in blood samples.…”

Section: To the Editormentioning

confidence: 99%