Page 56 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

54 CHAPTER 3 Immune assay assisted cancer diagnostic

methods. In a recent study, researchers have found three proteins of ERBB2, TNC,
and ESR1 for pancreatic ductal adenocarcinoma (PDA) which increases the AUC
from 0.86 to 0.97. Using this technique, CA19-9 was discovered to play an important
role in early cancer diagnosis [22,24,28].
Antibody-based microarray is also used for understanding the mechanism of
tumor progression. In bladder cancer, it is seen that 50%–70% of cancers recur after
standard transurethral resection. With the help of the antibody microarray method,
Srinivasan et al. have found 20 proteins that facilitated the tumor progression, lead-
ing to the prediction of recurrence with sensitivity of 80% and specificity of 100%.
They have also found repression of the TGF-β signaling pathway in recurrent cancer
[29]. They have reported that the signaling factors IFNG, TNF-α, and THBS1 were
expressed less, and the abundance of the inhibitor MAPK3 (also known as ERK1)
was higher, whilst SMAD2, SMAD3, and SMAD4 were again significantly under-
represented in these patients with bladder cancer. The data has indicated that TGF-β
signaling pathway inhibitors may reduce bladder cancer recurrence [29].
Gastric cancer (GC) has among the worse survival rates of any solid tumor.
Through using antibody microarrays, Puig-Costa et al. were able to detect numerous
biomarkers for GC, including 120 cytokines, 43 antigenic factors, 41 growth factors,
40 inflammatory factors, and 10 metalloproteinases [30]. This technique was used
because it has the ability to detect different proteins in a short span of time, it is
cost-effective and highly sensitive. This has also helped to discover of some biomark-
ers such as ICAM-1 and angiotensin that indicate a high inflammatory response in
gastric disease. It has been shown that monocyte chemotactic protein 1 (MCP-1) is
associated with tumor development in GC, and can be used as a specific biomarker
for GC patients. Antibody microarray analyses of GC has detected a 21-protein
inflammatory protein-driven gastric cancer signature (INPROGAS) that accurately
discriminates GC from noncancerous gastric mucosa, and may provide new leads
for the analysis of cancer progression. In 2017, Quan et al. have added 39 additional
markers, mostly consisting of cytokine, as it is understood that inflammation is a
specific feature of GC. They have included biomarkers such as TGF-β, TNF, and
mitogen-activated protein kinase (MAPK) signaling pathway, as a useful biomarker
for early-stage cancer diagnosis [31].
In another study, Schwenk et al. have used suspension bead array technology for
protein profile plasma in patients with prostate cancer and respective controls [32].
The results have indicated that carnosine dipeptidase 1 (CNDP1) plasma levels were
decreased in patients with prostate cancer, and subsequently they have founded an
association with aggressive prostate cancer. For increased sensitivity, a sandwich
immunoassay has been developed to investigate these findings in 1214 patients,
which has elucidated the association between decreased CNDP1 and lymph node
metastasis. In another investigation, CNDP1 levels were suggested to have a meta-
bolic role, as this investigation found reduced plasma levels of CNDP1 in cachexic
patients [32]
Miller et al. have reported comparison between two microarray methods; anti-
body microarray and hydrogel bed. They have found that antibody-based microarray