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potential of miRNA in lung cancer, the putative miRNA biomarkers reported vary with each
study even in cases when the same type of biofluid was used. A review by Brase et  al. [118]
discusses the putative circulating diagnostic miRNAs in different cancer types and highlights
variables such as sample size, number of miRNAs examined, technology used, and nor-
malization. All of these variables can influence the outcome, emphasizing the importance of
standardization and quality-controlled methods. Further illustrating the critical importance of
standardization and quality control, Kim et  al. retracted an article in which they had shown
that specific miRNAs are selectively destabilized depending on the adhesion status of the cells
[222] . The retraction was based on findings from the same laboratory that the RNA extraction
reagent biased the recovery of miRNAs with different GC content, highlighting the extrac-
tion method as an important variable that may contribute to the inconsistency of miRNA
biomarker findings. Standardized, quality-controlled collection, nucleic acid extraction, and
testing methods are of the utmost importance in enabling miRNA as robust and reliable bio-
markers and in expediting the transition of miRNA research to clinical practice.
5.5 CONCLUSIONS
A significant number of human protein coding genes are regulated by miRNAs. miRNA-
based therapies provide potentially attractive opportunities as these molecules can target mul-
tiple targets in different signaling pathways simultaneously. Furthermore, miRNAs are released
into the circulation, and measurement of such species in plasma, serum, and whole blood speci-
mens has shown early promise with respect to their acting as potential biomarkers for early dis-
ease detection, prognostic assessment, and companion diagnostic for therapeutic interventions.
In the near future, large, independent, well-characterized, family and population-based case-
control and additional validation studies are warranted to fully realize the potential of miRNAs
as biomarkers for disease diagnosis and predictive markers for targeted therapies.
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