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stage, accompanied by extensive invasion and lymphatic miR-181b and miR-182 were also found to be novel poor
metastasis. Thus, it is important to increase the prognosticators. Low expression of miR-125a-3p was
[37]
[56]
sensitivity and specifi city of diagnostic markers and/or associated with enhanced malignant potential, such as
to establish methods for GC treatment and prevention of tumor size, lymph node, and liver metastasis, and poor
GC. [38-40] prognosis, and this study suggested that miR-125a-3p
is a potent prognostic marker in GC. Furthermore,
[57]
miRNAs as novel diagnostic and prognostic miR-409-3p was found to be frequently down-regulated
biomarkers in GC
in patients with GC, and its expression was associated
Novel methods, such as circulating miRNA with distant metastasis. [58]
profi ling, have been suggested to be useful tools Clinical application of miRNAs in GC
for the non-invasive diagnosis of GC. Three serum
miRNAs (miRs-221/744/376c) were found to Some miRNAs have been shown to impact
distinguish GC patients from healthy controls with chemotherapy sensitivity if their levels were artifi cially
82.4% sensitivity and 58.8% specifi city. Moreover, up-regulated, others if they were down-regulated.
[41]
miR-221 and miR-376c demonstrated signifi cantly For instance, up-regulation of miR-21 or miR-106a
[59]
positive correlations with poor GC differentiation. In increased cisplatin resistance of GC cells, and Deng
[41]
[60]
a validation experiment, plasma levels of miR-451 and et al. showed that the up-regulation of miR-195
miR-486 were higher in patients with GC compared with or miR-378 led to enhanced 5-azacytidine resistance
healthy controls, with high area under the curve (AUC) in normal gastric cells. Up-regulation of miR-449 or
[42]
values (0.96 and 0.92). A genome-wide miRNA profi le miR-508-5p was demonstrated to positively impact
identifi ed high serum levels of miR-378 in patients sensitivity toward cisplatin (miR-449) or vincristine
[43]
with GC, and validation yielded a high AUC (0.86). or doxorubicin (miR-508-5p). [61,62] Interestingly, in
Quantitative real-time polymerase chain reaction analysis accordance with these fi ndings concerning the modulation
identifi ed 5 serum miRNAs (miR-1, miR-20a, miR-27a, of the sensitivity toward chemotherapeutic drugs via
[50]
miR-34, miR-423-5p) to be biomarkers for GC, and miRNAs, Bandres et al. reported that the up-regulation
their levels correlated with tumor stage. Plasma of miR-451 led to increased sensitivity of cancer cells
[44]
concentrations of miRNAs miR-17-5p, miR-21, toward radiotherapy by down-regulating macrophage
miR-106a and miR-106b were higher, whereas let-7a migration inhibitory factor MIF. Only one research
was lower in GC patients. AUC as high as 0.879 for the group reported the effect of miRNA down-regulation
[63]
[45]
miR-106a/let-7a ratio assay was achieved. High levels on chemotherapy resistance; Zhao et al. found that
of miR-17 and miR-106a in peripheral blood of GC increased doxorubicin sensitivity in GC cells was
patients confi rmed in another study, in which the AUC connected with down-regulation of miR-27a.
value for the combined miR-17/miR-106a assay was
[46]
0.741. These fi ndings suggest that miRNAs are useful Colorectal Cancer
biomarkers for early GC diagnosis. Colorectal cancer (CRC) is the 3rd most common cancer
and the 3rd leading cause of cancer-related death in the
miRNAs have recently been used to predict the outcome world, with an estimated incidence of one million new
of patients with GC. For example, a seven-miRNA cases and a mortality of > 500,000 deaths annually.
[13]
signature (miR-10b, miR-21, miR-223, miR-338, let-7a, The pathogenesis of CRC typically follows a protracted
miR-30a-5p and miR-126) was shown to be closely stepwise progression from benign adenoma to malignant
associated with relapse-free and overall survival (OS) adenocarcinoma and distant metastasis, rendering
[47]
among patients with GC. High expression of screening and early diagnosis as preferred options to ease
[48]
miR-20b, miR-150 and miR-93 or down-regulation the disease burden. This also highlights the need for
[49]
[64]
[51]
[50]
of miR-451 or miR-218 was also associated with the development of novel screening tools and diagnostic
poor survival, whereas there was a correlation between biomarkers.
miR-27a and lymph node metastasis. In addition,
[48]
Ueda et al. recently reported that miR-125b, miR-199a miRNAs as novel diagnostic and prognostic
[52]
and miR-100 represent a progression-related signature, biomarkers in CRC
whereas the low expression of let-7g and high expression [65]
of miR-214 were associated with shorter OS independent Ng et al. were the fi rst to report that circulating levels
of the depth of invasion, lymph node metastasis and of miRNAs differed in the blood plasma in CRC cases
and the controls. It was found that miR-92 was expressed
stage.
at higher levels in the plasma from CRC cases and could
Circulating miRNAs have been suggested to be distinguish cases from healthy control patients with 70%
useful prognostic markers of GC. High expression of specifi city and 89% sensitivity. Another study of 120 cases
circulating miR-17-5p/20a was an independent poor and 29 controls validated these fi ndings, showing that
prognostic factor. Low-level expression of let-7a/ levels of miR-92 can discriminate between CRC cases
[53]
[66]
let-7g/let-7f was associated with a poor prognosis. [54,55] and controls with 65% sensitivity and 82% specifi city.
146 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 3 ¦ October 15, 2015 ¦