UEGJournal Abstracts 2021 - 709

Liver & biliary
P0754
FIRST REPORT OF V-SET AND IMMUNOGLOBULIN DOMAIN
CONTAINING 1 EXPRESSION IN HEPATOCELLULAR CARCINOMA
P0755
INTERLEUKIN GENES ASSOCIATED WITH THE DEVELOPMENT
OF HEPATOCELLULAR CARCINOMA AS A RESULT OF VIRAL HEPATITIS
B AND C
S. Gurzu1, H. Sugimura2
1
, I. Jung1
George Emil Palade University of Medicine, Pharmacy, Sciences
and Technology, Pathology, Tirgu-Mures, Romania, 2
University School of Medicine, Tumor Pathology, Hamamatsu,
Japan
Contact E-Mail Address: simonagurzu@yahoo.com
Introduction: Understanding molecular pathways is critical to the implementation
of antibody-based immunotherapy protocols. The cell surface
protein V-set and immunoglobulin domain containing 1 (VSIG1) is considered
a " gastric-specific antibody " with role in cell-cell adhesion and its
potential involvement in carcinogenesis and evolution of hepatocellular
carcinoma (HCCs) was not proved yet.
Aims & Methods: This is the first report about the potential clinical value
of VSIG1 in HCC. In order to prove its possible prognostic or predictive
value, the immunohistochemical (IHC) expression of VSIG1 was checked
in 105 consecutive HCCs and correlated with the clinicopathological parameters,
same as with E-cadherin and vimentin expression. The miRNET
was also explored, to understand the possible mechanism of interaction
between the above-mentioned encoding genes.
Results: IHC positivity of VSIG1 was revealed by 50/105 (55.24%) differentiated
(G1/2) HCCs diagnosed in pT1/2 stages, being strongly correlated
with E-cadherin expression (p=0.004; Spearman r = 0.19 and Pearson r =
0.21). Vimentin positivity was expressed by 17 cases (36.2%), all of them
being negative for VSIG1. A negative correlation was also proved between
E-cadherin and vimentin (p=0.005). The miRNET interaction network examination
revealed that VSIG1, vimentin and CDH1 gene (which encodes
E-cadherin) are interconnected by miR-200b-3p, a key regulator of epithelial
mesenchymal transition (EMT) phenomenon. VSIG1 overexpression
proved to be an independent prognostic parameter; loss of VSIG1 was an
indicator of tumor cells dedifferentiation, vascular invasion and shorter
overall survival rate (p=0.007).
Conclusion: As the molecular therapeutic approach of HCC is far to be elucidated,
finding new potential targeted pathways can help development
of new potential strategies of management. As E-cadherin/VSIG1 complex
of adherens junction proteins seems to suppress HCC dedifferentiation,
restauration of its integrity might help keeping cell-cell contact and prevent
EMT phenomenon.
This study was partially supported by the Romanian National Authority
for Scientific Research, CNCS - UEFISCDI, project number 20 PCCF/2018,
code: PN-III-P4-ID-PCCF-2016-0006
Disclosure: Nothing to disclose.
V. Pryshchepenka1
Hamamatsu
A. Kakoichankava5
1
, H. Yupatau2, V. Pryshchepenka3
, V. Akulich4
Vitebsk State Order of Peoples' Friendship Medical University
(VSMU), Propedutics of Internal Diseases Chair, Vitebsk, Belarus,
2
Vitebsk State Order of Peoples' Friendship Medical University
(VSMU), Propaedeutics of Internal Diseases Department, Vitebsk,
Belarus, 3
Vitebsk State Order of Peoples' Friendship Medical
University (VSMU), Educational Center, Vitebsk, Belarus, 4
Vitebsk
State Order of Peoples' Friendship Medical University (VSMU),
Clinical Microbiology, Vitebsk, Belarus, 5
Vitebsk State Order of
Peoples' Friendship Medical University (VSMU), Vitebsk, Belarus
Contact E-Mail Address: Prslava92@gmail.com
Introduction: The development of liver diseases is based on immune
mechanisms associated, among other things, with a violation of the cytokine
profile of patients. Genetic association analysis of a well-characterized
HBV cohort revealed that one of IL10 haplotypes, IL10-ht2, was
strongly associated with hepatocellular carcinoma (HCC) occurrence in
gene dose-dependent manner1
.
The role of interleukins 1, 2, 6, 18, 33 and others has been shown in patients
with hepatocellular carcinoma2
. However, not all mechanisms of
development of hepatocellular carcinoma are known.
Aims & Methods: Aim of our study is determine the most important interleukin-linked
pathways associated with hepatocellular carcinoma in pftients
with HBV and HCV. The genetic characteristics of patients with liver
diseases were determined by comparative analysis of gene expression in
liver tissues obtained by liver biopsy. Samples of patients with liver diseases
were formed: patients with hepatocellular carcinoma due to viral
hepatitis B (HCC-HBV) - 10 people, patients with hepatocellular carcinoma
due to hepatitis C (HCC-HCV) - 72 people.
The group of patients without liver affection included 24 people. Transcriptom
analisys console 4.0 (Thermo Fisher Scientific inc.) and Openaccess
databases E-GEOD-17548, 19665, 14323, 17967, 58979, 59492 were
used for analisys.
Results: Patients with HCC-HBV showed increased expression of 4586
genes (8.4%) and decreased expression of 756 (14.15%) genes compared
with patients without liver affection. Among the signaling pathways associated
with the activity of interleukins, the largest number of genes is
involved in the Interleukin-11 signaling pathway. Under the influence of
interleukin-11, 13 genes are hyperexpressed (significance - 2.46), including
IL-6 ST, JAK1, STAT1, PIA S1, ITGA2, which ultimately leads to the transformation
of CD4 cells along the Th2 pathway, an increase in macrophage
activity, activation of antiapoptotic mechanisms, etc.
An increase in the activity of Interleukin -7 is also observed, leading to an
increase in the activity of JAK1 (significance - 0.37), Interleukin-12, -23,
also leading to hyperexpression of JAK1 and STAT1 (significance - 2.02).
The most significant interleukins involved in the regulation of the JAK1,
STAT1, 3, 6 genes are IL-4 and IL-13 (significance, 14.44). In patients with
HCC-HBV, there is an increased expression of JAK1 and a decreased expression
of IL-13RA2.
In patients with HCC-HCV, there is an increased expression of 4330 (7.93%)
genes and a decreased expression of 693 (1.27%) genes compared to
group of patients without liver affection. Among the signaling pathways
associated with the activity of interleukins, as well as in patients with
HCC-HBV, the largest number of genes is involved in the Interleukin-11 signaling
pathway. Under the influence of interleukin-11, 9 genes are overexpressed
(significance - 1.24), including STAT1, PIA S1, and hypoexpresVol.
9 | October 2021
709
,
UEGJournal Abstracts 2021

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