Biology Reference
In-Depth Information
[ 32 ]. However, in a follow-up study miR-29b, miR-29c, miR-181a, and miR-181b
were included in a miRNA-based molecular classifier that could distinguish
between indolent CLL and aggressive CLL with or without 11q deletion [ 40 ] . The
same report showed that miR-29b and miR-181b targets the TCL1 (T-cell leuke-
mia/lymphoma 1A) oncogene, overexpression of which may be a causal event in
the pathogenesis of CLL [ 40 ], suggesting a key role for miR-29 and miR-181 fam-
ily members in CLL.
Loss of miR-181b expression was associated with therapy-refractory CLL in a
separate study, which also found that low miR-181b expression and high miR-21
expression were significant independent prognostic factors for poor overall survival
and for time to disease progression [ 137 ] . Another study identi fi ed 32 miRNAs that
could distinguish subtypes of CLL with distinct common genomic aberrations: 11q
deletion, 17p deletion, trisomy 12, 13q deletion, and normal karyotype, respectively
[ 138 ]. Interestingly, this study revealed that low expression of miR-181a was asso-
ciated with aggressive disease in patients with 17p deletion, but with less aggressive
disease in patients with trisomy 12, demonstrating that individual miRNAs may
have subtype-specific biomarker roles.
The prognostic value of miR-29 for CLL was independently confirmed in a study
by Stamatopoulos et al . who showed that miR-29c and miR-223 were downregu-
lated in advanced stage CLL and that both miRNAs significantly predicted treat-
ment-free survival and overall survival [ 139 ]. The same authors developed a
RT-qPCR-based test for risk stratification of patients diagnosed with early stage
CLL, which combined four prognostic markers: miR-29c, miR-223, ZAP70, and
lipoprotein lipase (LPL) [ 139 ]. Each marker was dichotomized based on expression
levels and the markers were combined to generate a simplified risk score ranging
from 0 (low risk for all four markers) to 4 (high risk for all four markers). The study
demonstrated that increased accuracy of predictions can be obtained by combining
different types of biomarkers into a molecular diagnostic test. Similarly, Rossi et al .
developed a three-marker test named the 21FK score, which combined information
on miR-21 expression levels, 17p deletion status, and karyotype status (normal or
abnormal) to produce a three-category risk score (0, 1, or 2) that could stratify CLL
patients according to overall survival times [ 137 ]. The 21FK risk score was superior
to routine prognostic factors for prediction of overall survival time in two indepen-
dent CLL patient cohorts [ 137 ], suggesting that such a test could have clinical utility
in the future. Translation of molecular diagnostic tests to actual clinical practice,
however, requires substantial independent validation in large prospective multi-
center studies generally including thousands of patients.
13.3.4
Prostate Cancer
Prostate cancer (PC) is the most frequently diagnosed malignancy in men in Western
countries and a major cause of cancer-associated death. The natural history of PC is
highly variable. Some PCs develop slowly and do not cause significant symptoms
during the remaining lifetime of the patient, while other PCs progress more rapidly,
Search WWH ::




Custom Search