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The final expression level and sequence of the mature miRNA in a given cancer
cell depend on the cooperation and net effect of all of these, and possibly other yet
to be described mechanisms [
85
] . The disease-speci fi c expression patterns of
miRNAs as well as their key functional roles in tumorigenesis suggest that miRNAs
hold great potential as cancer biomarkers and in some cases also as therapeutic
targets.
13.2
MicroRNA Pro fi ling for Discovery of Cancer Biomarkers
13.2.1
Molecular Pro fi ling of miRNA Expression in Cancer
Tissue Samples
Profiling of miRNAs expression in clinical tumor tissue samples has become a
widely used approach for discovery of new cancer biomarker candidates, including
diagnostic, prognostic, and predictive biomarkers [
86-
88
]. High stability of miR-
NAs in freshly frozen, as well as archived formalin-fixed paraffin-embedded (FFPE),
tissue samples [
89
] has made miRNAs particularly attractive for cancer biomarker
studies. In contrast, mRNAs are quickly degraded upon formalin-fixation, making
mRNA expression analysis based on FFPE samples rather difficult. Moreover,
because FFPE samples are collected as part of daily clinical routines and stored long
term at hospital pathology departments, such samples are generally more readily
available than freshly frozen samples from patient cohorts with long-term clinical
follow-up information. New miRNA markers may enable earlier detection of can-
cer, which is critical for a favorable outcome. Furthermore, molecular subclassi fi cation
of tumors based on miRNA expression patterns may be used to guide individualized
treatment of cancer, e.g., by allowing stratification of patients into subgroups with
low or high risk of disease progression. Expression profiling can also facilitate the
discovery of miRNAs with key regulatory roles in cancer development or progres-
sion and thereby can lead to the identification of potential new treatment targets
[
26
] .
Figure
13.2
outlines a frequently used strategy for molecular profiling of cancer.
In this example, miRNA expression is compared in two sample groups, tumor vs
.
normal tissue, for identification of diagnostic biomarker candidates. Alternatively,
miRNA expression may be analyzed in tumor samples from patients with aggres-
sive vs
.
indolent (slowly growing, nonaggressive) cancer, or from patients respon-
sive or nonresponsive to a certain anticancer drug in order to identify candidate
markers with prognostic or predictive biomarker potential, respectively. Depending
on the research question addressed, additional sample groups can be included.
Ideally, screening for differentially expressed miRNAs between sample groups
should be performed in one patient set followed by validation in at least one inde-
pendent patient sample set to ensure reproducibility and selection of meaningful
candidates for further biomarker validation studies.
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