Preanalytical, Analytical and Postanalytical Considerations in Circulating MicroRNAs Measurement

Overview

Journal Biochem Med (Zagreb)

Specialty Biochemistry

Date 2024 Jun 17

PMID 38882585

Authors

Mustapha Zendjabil

Affiliations

Soon will be listed here.

Abstract

Microribonucleic acids (miRNAs) have emerged as a new category of biomarkers for many human diseases like cancer, cardiovascular and neurodegenerative disorders. MicroRNAs can be detected in various body fluids including blood, urine and cerebrospinal fluid. However, the literature contains conflicting results for circulating miRNAs, which is the main barrier to using miRNAs as non-invasive biomarkers. This variability in results is largely due to differences between studies in sample processing methodology, miRNA quantification and result normalization. The purpose of this review is to describe the various preanalytical, analytical and postanalytical factors that can impact miRNA detection accuracy and to propose recommendations for the standardization of circulating miRNAs measurement.

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References

Mompeon A, Ortega-Paz L, Vidal-Gomez X, Costa T, Perez-Cremades D, Garcia-Blas S . Disparate miRNA expression in serum and plasma of patients with acute myocardial infarction: a systematic and paired comparative analysis. Sci Rep. 2020; 10(1):5373. PMC: 7096393. DOI: 10.1038/s41598-020-61507-z. View

Donati S, Ciuffi S, Brandi M . Human Circulating miRNAs Real-time qRT-PCR-based Analysis: An Overview of Endogenous Reference Genes Used for Data Normalization. Int J Mol Sci. 2019; 20(18). PMC: 6769746. DOI: 10.3390/ijms20184353. View

Kirschner M, Kao S, James Edelman J, Armstrong N, Vallely M, van Zandwijk N . Haemolysis during sample preparation alters microRNA content of plasma. PLoS One. 2011; 6(9):e24145. PMC: 3164711. DOI: 10.1371/journal.pone.0024145. View

Ward Gahlawat A, Lenhardt J, Witte T, Keitel D, Kaufhold A, Maass K . Evaluation of Storage Tubes for Combined Analysis of Circulating Nucleic Acids in Liquid Biopsies. Int J Mol Sci. 2019; 20(3). PMC: 6387045. DOI: 10.3390/ijms20030704. View

Dufourd T, Robil N, Mallet D, Carcenac C, Boulet S, Brishoual S . Plasma or serum? A qualitative study on rodents and humans using high-throughput microRNA sequencing for circulating biomarkers. Biol Methods Protoc. 2020; 4(1):bpz006. PMC: 7200924. DOI: 10.1093/biomethods/bpz006. View

Ford K, Anwar M, Heys R, Ahmed E, Caputo M, Game L . Optimisation of laboratory methods for whole transcriptomic RNA analyses in human left ventricular biopsies and blood samples of clinical relevance. PLoS One. 2019; 14(3):e0213685. PMC: 6417664. DOI: 10.1371/journal.pone.0213685. View

Dellett M, Simpson D . Considerations for optimization of microRNA PCR assays for molecular diagnosis. Expert Rev Mol Diagn. 2016; 16(4):407-14. DOI: 10.1586/14737159.2016.1152184. View

McDonald J, Milosevic D, Reddi H, Grebe S, Algeciras-Schimnich A . Analysis of circulating microRNA: preanalytical and analytical challenges. Clin Chem. 2011; 57(6):833-40. DOI: 10.1373/clinchem.2010.157198. View

Liu P . MicroRNA Expression Analysis: Next-Generation Sequencing. Methods Mol Biol. 2018; 1783:171-183. DOI: 10.1007/978-1-4939-7834-2_8. View

10.

Varallyay E, Burgyan J, Havelda Z . MicroRNA detection by northern blotting using locked nucleic acid probes. Nat Protoc. 2008; 3(2):190-6. DOI: 10.1038/nprot.2007.528. View

11.

Saleh A, Soliman S, Habib M, Gohar S, Abo-Zeid G . Potential value of circulatory microRNA122 gene expression as a prognostic and metastatic prediction marker for breast cancer. Mol Biol Rep. 2019; 46(3):2809-2818. DOI: 10.1007/s11033-019-04727-5. View

12.

Sourvinou I, Markou A, Lianidou E . Quantification of circulating miRNAs in plasma: effect of preanalytical and analytical parameters on their isolation and stability. J Mol Diagn. 2013; 15(6):827-34. DOI: 10.1016/j.jmoldx.2013.07.005. View

13.

Grasedieck S, Scholer N, Bommer M, Niess J, Tumani H, Rouhi A . Impact of serum storage conditions on microRNA stability. Leukemia. 2012; 26(11):2414-6. DOI: 10.1038/leu.2012.106. View

14.

Kappel A, Keller A . miRNA assays in the clinical laboratory: workflow, detection technologies and automation aspects. Clin Chem Lab Med. 2016; 55(5):636-647. DOI: 10.1515/cclm-2016-0467. View

15.

Binderup H, Houlind K, Madsen J, Brasen C . Pre-storage centrifugation conditions have significant impact on measured microRNA levels in biobanked EDTA plasma samples. Biochem Biophys Rep. 2017; 7:195-200. PMC: 5613297. DOI: 10.1016/j.bbrep.2016.06.005. View

16.

Xiang M, Zeng Y, Yang R, Xu H, Chen Z, Zhong J . U6 is not a suitable endogenous control for the quantification of circulating microRNAs. Biochem Biophys Res Commun. 2014; 454(1):210-4. DOI: 10.1016/j.bbrc.2014.10.064. View

17.

Buschmann D, Haberberger A, Kirchner B, Spornraft M, Riedmaier I, Schelling G . Toward reliable biomarker signatures in the age of liquid biopsies - how to standardize the small RNA-Seq workflow. Nucleic Acids Res. 2016; 44(13):5995-6018. PMC: 5291277. DOI: 10.1093/nar/gkw545. View

18.

Benz F, Roderburg C, Cardenas D, Vucur M, Gautheron J, Koch A . U6 is unsuitable for normalization of serum miRNA levels in patients with sepsis or liver fibrosis. Exp Mol Med. 2013; 45:e42. PMC: 3789266. DOI: 10.1038/emm.2013.81. View

19.

Khan J, Lieberman J, Lockwood C . Variability in, variability out: best practice recommendations to standardize pre-analytical variables in the detection of circulating and tissue microRNAs. Clin Chem Lab Med. 2017; 55(5):608-621. DOI: 10.1515/cclm-2016-0471. View

20.

Pritchard C, Cheng H, Tewari M . MicroRNA profiling: approaches and considerations. Nat Rev Genet. 2012; 13(5):358-69. PMC: 4517822. DOI: 10.1038/nrg3198. View