microRNA Biomarkers as Potential Diagnostic Markers for Cancer - Genomic Biomarkers for Pharmaceutical Development - page 102

regression model comprised of nine miRNAs (miR-18a, -24, -30a-3p, -92a, -342-3p, -99b, -106b,
-42-3p, and -532-3p), which predicted with 89% sensitivity and 100% specificity which cyst
fluid specimen came from a cyst requiring resection or more conservative management.
The studies suggest that miRNA signatures may complement KRAS / GNAS combination
and become a powerful tool that can help clinicians achieve a confirmatory diagnosis and
guide patient management decisions ( Fig. 5.3 ). However, prospective multi-center testing of
signatures using EUS-FNA specimens will be essential to confirm their clinical application.
5.3.1.3 Prognosis
Prognosis for patients with pancreatic cancer can be affected by many factors, such as the can-
cer type, stage and grade (indicative of aggressiveness and metastases), the patient's age and
general health, or the effectiveness and risk of treatment options. Studies interrogating prognos-
tic capabilities of miRNAs have yielded a handful of candidates that predict patient outcome.
Perhaps the most studied prognostic miRNA candidate is miR-21. Patients with pancreatic
cancer and high expression of miR-21, as compared to patients with low expression of miR-21,
have a shorter survival in both the metastatic and the adjuvant settings, and are often resist-
ant to gemcitabine treatment [88] , [111] . Furthermore, miR-21 expression levels in PDAC tissue
specimens were shown to be correlated with pre-operative serum levels of CA 19-9 (r = 0.63,
p = 0.0022) [112] . Similarly, increased expression levels of miR-196a-2 in tissue [86] and serum
[113] specimens from patients with PDAC were associated with a significantly shorter median
survival as compared to patients with low levels of those miRNAs, and predicted patient
tumor resectability [113] . Another study reported that low levels of miR-10b in FNA samples
collected from patients who underwent neoadjuvant therapy were associated with improved
response to gemcitabine-based neoadjuvant therapy, longer time to metastasis and improved
overall survival of 50% after two years [114] . It appears that miR-10b could be used as an indi-
cator of localized pancreatic disease, similarly to miR-143 expression which was negatively cor-
related with lymph nodes spreading (r = −0.64; p = 0.0004) [112] . Two groups reported miRNA
signatures that showed utility in predicting survival in patients with nodal disease. The miR-
NAs in these signatures did not overlap and included: miR-452, miR-105, miR-127, miR-518a-2,
miR-187 and miR-30a-3p [86] , as well as miR-155, miR-203, miR-210 and miR-222 [91] .
5.3.2 miRNAs in Biofluids
Cancer is currently the third leading cause of human mortality after heart disease and
infectious diseases. However, cancer mortality is expected to surpass that of cardiovascular
diseases by the year 2020 [115] . Evidence has shown that most cancers including breast, colo-
rectal (CRC) and melanoma are treatable if detected early. Consequently, the development
of non-invasive, early-detection biomarkers for the diagnosis of multiple human cancers has
been a major area of focus.
Circulating biomarkers which are present in blood offer advantages over image-based
diagnostics, such as the following:
1. They are minimally invasive.
2. They can be monitored frequently over time in a subject to establish an accurate baseline.
3. They have relatively low cost compared to imaging procedures.