41
| 2 | 2011
Klinisk Biokemi i Norden
(
Fortsætter side 42)
similar to the profile of troponin release (34). Since
then miRNA cardiac biomarkers have also been identi-
fied in human subjects, including in patients with AMI
(35),
HF (36), and stable coronary artery disease (37),
confirming the potential of miRNA as a new group
of cardiac markers. Still, the clinical utility of miRNA
biomarkers has not been established, and this should be
examined according to predefined criteria (Table; modi-
fied from ref. 38). The analytical accuracy and stability
is clearly a concern, and there is also a lack of consensus
on normalization (“housekeeping miRs”). Furthermore,
the extraction of RNA from serum and plasma is time
consuming and may introduce pre-analytical variation
if not performed correct. This, combined with the easy
handling and proven accuracy of protein markers for
diagnosing AMI and HF, makes the use of miRNA bio-
markers in the acute setting unlikely. Still, biomarkers
can also provide information on prognosis, subclassi-
fication of patients according to pathophysiology, and
the selection of patients to therapy (38), areas in which
novel markers could prove important. However, the
clinical relevance of miRNA biomarkers over established
risk models and protein markers should be examined
by several statistical methods, including multivariate
logistic regression models, receiver operating statistics,
and by the novel statistical metrics for evaluating model
fit (39). To be of real clinical utility, the new biomarker
should also improve patient care, thus provide the phy-
sician with a tool for titration of drug doses, selection
to invasive procedures, and to guide patient follow-up.
This is currently not possible with miRNA biomarkers
as there is a lack of knowledge on the kinetics of and
the factors that alter miRNA biomarkers. Thus, similar
to the status of miRNA based therapy, there are still
several important issues that should be addressed before
miRNA biomarkers can be considered for clinical use.
Conclusion
The discovery of miRNAmolecules as powerful regula-
tors of mRNA function has improved our understand-
ing of protein synthesis control. Basic researchers have
reported impressive alterations in animal function by
miR gain- and loss-of-function studies, but the clinical
implications of these results for therapy and diagnosis
is not clear. Future miRNA research should focus on
experimental models to promote our understanding
of miRNA regulation and function, and on clinical
studies to validate results of the experimental models
in human subjects.
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