microRNA Biomarkers as Potential Diagnostic Markers for Cancer - Genomic Biomarkers for Pharmaceutical Development - page 109

breast cancer patients, suggesting that these miRNAs could serve as useful screening mark-
ers for breast cancer [174] .
More recently, another large study involving plasma from over 269 breast cancer patients
[with and without circulating tumor cells (CTC)], including 76 controls, showed that miR-
200b could distinguish plasma of circulating tumor cell (CTC)-positive patients from that of
CTC-negative patients [175] . The association of miR-200b with CTC, an established prognos-
tic marker for metastatic breast cancer, suggests that this miRNA could be also be used as a
prognostic marker for breast cancer. Other miRNAs shown to be reportedly higher in the CTC
positive patients include miR-141, miR-20a, miR-200c, miR-375, miR-203, miR-210, and miR-
801. miR-21 is one of the most commonly up-regulated miRNA in most cancer types, and it
was expressed at higher levels in sera of breast cancer patients than in sera of controls [176] .
Similarly to the different sets of circulating miRNAs that have been identified in lung cancer
patients, it is notable that there is no consensus in the circulating miRNA findings in breast
cancer.
5.3.2.5 Gastric Cancer
Gastric cancer, commonly referred to as stomach cancer, is a highly prevalent type of can-
cer in most parts of the world. It is one of the most common causes of cancer death world-
wide and causes about 738,000 deaths annually [177] . Part of this high mortality rate may
be due to the fact that the molecular mechanisms leading to gastric cancer are not yet fully
understood. miRNAs have been implicated in gastric cancer and associated with cancer type,
stage, and survival [178] . Ueda et al. identified differentially expressed miRNAs in 160 paired
tumor and normal tissues from gastric patients [179] . An analysis by Valladares-Ayerbes et al.
of the dataset published by Ueda et al. revealed that miR-200 was not differentially expressed
in the paired non-tumor and cancer samples; however, they found that miR-200c was signifi-
cantly (p = 0.012) higher in blood samples from gastric cancer patients (N = 52) compared to
controls (N = 15) [180] . The increase in miR-200c levels was also associated with poor over-
all survival, suggesting that miR-200c is a potential circulating prognostic marker for gastric
cancer. Another potential diagnostic and prognostic miRNA marker, miR-196a, was reported
by Tsai et al [181] . miR-196a was found to be up-regulated in gastric cancer tissues compared
to normal tissues, and high levels of serum miR-196a was associated with recurrence of gas-
tric cancer [181] .
Circulating miRNA markers with prognostic and therapeutic potential for gastric cancer
have also been identified. Wang et al. identified miR-17-5p and miR-20a in pre- and post-
operative gastric cancer patients, and reported that the miRNA pair was associated with dif-
ferentiation status and TNM stage of gastric cancer [182] . Wang et al. also showed that, in
a mouse tumor model, tumors regressed after the mice were treated with antagomirs (syn-
thetic oligonucleotides designed to reduce or abolish miRNA activity) specifically targeted
at miR-17-5p and miR-20a. Serum levels of the two miRNAs were also reduced in mice that
were treated and that showed tumor regression [182] , further suggesting that this pair of
miRNAs could also be used for monitoring therapy response. In an effort to identify diag-
nostic markers for gastric cancer, Liu et al. used qRT-PCR assays to screen serum of gastric
cancer patients and controls, and reported that miR-378 was able to distinguish gastric can-
cer from controls with an AUC of 0.86 and sensitivity and specificity of 87.5% and 70.73%,
respectively [183] . miR-21 has been shown to be up-regulated in most cancers, and exerts its