microRNA Biomarkers as Potential Diagnostic Markers for Cancer - Genomic Biomarkers for Pharmaceutical Development - page 107

patients, and further that these miRNAs were associated with poor survival [153] . On the
other hand, Yuxia et al. examined serum levels of miR-125b in 193 NSCLC patients before
and after surgery and therapy, and found that serum miR-125b distinguished NSCLC
patients from the control group with an AUC of 0.786 [154] . In addition, multivariate analy-
sis revealed that high expression of miR-125b was significantly (p<0.0001) associated with
poor prognosis. Le et al. also examined serum miRNAs from pre- and 10 days post-surgery
in 82 NSCLC patients, and found that levels of miR-21, miR-205, miR-30d, and miR-24 were
increased in those with lung cancer relative to controls [155] . Additionally, levels of miR-
21 and miR-24 were reduced in post-operative samples compared to pre-operative serum
samples.
miRNAs have not only been shown to be useful as diagnostic markers, but miRNA
expression levels have also been demonstrated to change with cancer progression. For exam-
ple, Zheng et al. showed that miR-155 and miR-197 were higher in the plasma of lung can-
cer patients with metastatic disease than those with localized tumors [156] . As discussed
above, a successful biomarker in lung cancer must have the ability to distinguish benign lung
tumors from invasive tumors. miRNAs have also shown promise in this area, with Shen et al.
having showed that a combination of three plasma miRNAs (miR-21, miR-210, and miR-
486-5p) could distinguish malignant solitary pulmonary nodules from benign nodules [157] .
Roth and coworkers showed that serum levels of miR-10b, miR-141 and miR-155 could also
distinguish lung cancer from benign disease [158] . Similarly, Xie et al. showed that serum
miR-24, miR-26a, and miR-30d could distinguish malignant form benign lung disease, in
addition to predicting response to docetaxel [159] .
In this era of emerging personalized medicine, there has been an increased interest in
predictive biomarkers. miRNAs have been shown to predict response to chemotherapy in
NSCLC patients. Specifically, Wei et al. examined miR-21 in 30 healthy controls and 63 lung
cancer patients, including 11 with partial chemotherapy response and 24 with stable and pro-
gressive disease [160] . miR-21 was not only found to be diagnostic, but also highly associated
with response to platinum-based chemotherapy response. The group with partial response
had much lower levels of miR-21 than the group that included patients with stable disease
and patients with progressive disease. In a study involving 78 NSCLC patients and 48 con-
trols, Silva et al. revealed five plasma miRNAs (let-7f, miR-20b, miR-30e-3p, miR-223, and
miR-301), combinations of which were either diagnostic or prognostic for NSCLC [161] .
While all of the studies on circulating miRNA in lung cancer highlight the great promise and
potential of miRNAs as diagnostic, prognostic, and even predictive biomarkers, the lack of
consensus among the results is worrisome and is discussed in the final section of this review
regarding the challenges of miRNAs as biomarkers.
5.3.2.4 Breast Cancer
Breast cancer, the leading cause of cancer mortality in women worldwide [162] , has been
one of the most studied cancers in terms of circulating miRNA. Although breast cancer mor-
tality has been significantly reduced with the introduction of mammograms [163] , about
30% of the cases are still diagnosed at a stage that involves regional lymph nodes, with ~62%
being detected at a localized stage [164] . In addition, in some parts of the world, women have
limited access to annual mammograms. Consequently, the development of a cost-effective,
early-detection assay for breast cancer is still an area of active research.