microRNA Biomarkers as Potential Diagnostic Markers for Cancer - Genomic Biomarkers for Pharmaceutical Development - page 106

0.772, respectively. In addition, a significant correlation between miR-196a and the maximum
tumor diameter (Spearman r = 0.516, p = 0.041) was uncovered.
These exciting 'proof of principle' studies show the feasibility of developing sensitive and
specific blood-based miRNA molecular testing for detection of pancreatic cancer. These tools
could eventually be applied clinically, provided that their performance characteristics can be
confirmed in independent, well-controlled, large prospective multi-center studies.
5.3.2.3 Lung Cancer
The majority (70%) of all lung cancer diagnoses are detected at late stages, involving
regional or distant metastatic disease. This late diagnosis contributes to a high mortality rate,
with an overall five year survival rate of less than 15% [139] . Unlike CRC and breast cancer,
which have screening programs [140,141] , lung cancer does not have an approved annual
screening method. A recent prospective study by the National Lung Cancer Screening Trial
(NLST) revealed a 20.3% decrease in lung cancer mortality in the low-dose CT screening
arm of the trial compared to the control arm screened by chest X-ray [142] . As a result, the
National Comprehensive Cancer Network has updated its screening guidelines to include
low-dose CT for those at risk of lung cancer. However, there are challenges in terms of over-
diagnosis due to the detection of otherwise non-lethal / benign lesions of the lung. Apart from
the high cost, there are concerns about risk of repeated exposure to radiation, as positive CT
results have to be followed by periodic CT scans every six months or more often if needed.
Therefore, there is an urgent need to identify biomarkers that can be used as alternative non-
invasive screening tools. Differential expression of miRNAs in lung cancer tissues compared
to normal lung tissue has been extensively studied and is well-demonstrated, especially in
the case of the let-7 family of miRNAs [143] . However, only in recent years have circulating
miRNAs from biofluids, such as whole blood, plasma, serum, and sputum, been examined as
potential diagnostic markers for lung cancer [144,145] . Some noteworthy studies on circulat-
ing miRNAs in lung cancer are highlighted below.
A study by Shen and coworkers involving a total of 86 NSCLC and 57 controls revealed a
four-miRNA panel in plasma, including miR-126, which distinguished NSCLC from healthy
controls with a sensitivity and specificity of 73% and 96%, respectively [146] . Using whole
blood, Keller and coworkers showed that miR-126 and miR-98 were among the top miRNAs
that could distinguish NSCLC from healthy controls [147] . Other recent studies by Foss and
coworkers showed serum miR-1254 and miR-574-5p were differentially expressed between
NSCLC (N = 33) and healthy controls (N = 42) [148] . Work by Chen et al. showed that miR-
205, miR-25, and miR-223 were up-regulated in serum from NSCLC patients when compared
to healthy controls [149] . In 2009, Rabinowits and coworkers reported elevated levels of miR-
155 and miR-21 in circulating tumor-derived exosomes in the plasma of lung cancer patients
[150] . Using 50 serum specimens (20 healthy controls and 30 NSCLC) as the training set and
130 specimens (75 healthy controls and 55 NSCLC), we showed that the differential expres-
sion of miR-15b and miR-27b was able to discriminate NSCLC from healthy controls [151] .
Using a cross-validation method, Patnaik et al. showed that miR-190b, miR-630, miR-942, and
miR-1284 in whole blood were the most commonly used miRNAs in the classifier generated
for distinction of lung adenocarcinoma from healthy controls [152] .
In yet another recent study, Wang and coworkers revealed altered expression of five miR-
NAs (miR-93, miR-100, miR-151, miR-134, and miR-345) in pleural effusions of 184 NSCLC