TY  - GEN
AV  - public
A1  - Shahryarhesami, Soroosh
TI  - Detection of bacteria and virus-associated
Pancreatic Ductal Adenocarcinoma by
cell-free protein microarray
CY  - Heidelberg
N2  - Summary
Background
Infection is the cause of nearly 20% of all cancers. Infectious agents such as the bacterium
Helicobacter pylori (H. pylori) as the first known bacterial carcinogen and viruses from
Herpesviridae family are involved in the pathogenesis of different cancers. Screening for
antibodies against bacterial and viral antigens in cancer patients may therefore uncover
potential markers and targets for optimized cancer control strategies. To these ends, I
studied the antibody composition in the peripheral blood of patients with pancreatic ductal
adenocarcinoma (PDAC) and appropriate non-cancer donors as controls.
Methods
All 1437 open reading frames (ORFs) of H. pylori and the 100 ORFs of Turkey herpesvirus
(HVT) were produced by two successive PCRs and spotted on nickel-coated glass surfaces. By
in vitro transcription-translation, whole-proteome microarrays were produced for H. pylori
and HVT. Immunoassays were performed with PDAC and non-PDAC serum samples to detect
antibody binding patterns and to differentiate between PDAC and non-PDAC groups. For
presenting the association pattern of each detected antigen with PDAC, the result was
calculated as Odds Ratio (OR) with 95% Confidence Interval (CI). Also, functional annotations
were performed.
Results
At first, the H. pylori proteome was screened using serum pools of 10 PDAC, 10 healthy and
9 CP (chronic pancreatitis). A total of 46 proteins were detected, of which 29 showed
association to PDAC (OR>1). After screening for candidates in the serum pools, individual
serum samples of PDAC and non-PDAC (healthy and CP) were applied to the microarray. In
total, 47 PDAC and 38 non-PDAC samples (19 healthy and 19 CP) were analyzed. A total of
62 proteins were detected. Most of them showed association to PDAC (OR>1); 33 antigens
had also been found in the pool experiments, such as HP0874, HP0599 and HP0175. In
further experiments, 11 PDAC and 8 non-PDAC serum pools with gastrointestinal conditions
were applied to find H. pylori positive antigens. In total, 59 antigens were detected in this
experiment of which 29 showed association to PDAC (OR>1).
The HVT proteome was firstly screened using serum pools (10 PDAC, 10 healthy and 10 CP).
In this step, three antigens were detected in PDAC pools. Subsequently, screening was
performed using individual samples. Altogether, 74 PDAC and 46 non-PDAC serum samples
(24 CP patients and 22 healthy donors) were applied to the HVT microarray. In total, 25 HVT
candidates were identified including the antigens which were detected in the pools:
HVT079, HVT059 and HVT062.
Conclusions
H. pylori and HVT screenings were performed to find antigens which are associated with the
occurrence of PDAC using serum pools and individual serum samples. Each screening
produced a candidate list, which is a valuable resource for diagnostic purposes. Among the64
167 H. pylori detected antigens, four antigens were detected in all three datasets with strong
association to PDAC: HP0874, HP0010, HP0601 and HP01238. Among the 25 HVT proteins
that were detected, three were detected commonly: HVT079, HVT059 and HVT062. These
results could help PDAC diagnostics and provides targets for interfering with PDAC
development and progression.
Y1  - 2020///
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/28115/
ID  - heidok28115
ER  -