CATENIN-δ-1 AS A POTENTIAL MARKER OF GASTRIC CANCER IN A SAMPLE OF IRAQI PATIENTS WITH GASTRIC DISEASES ASSOCIATED WITH HELICOBACTER PYLORI

Abstract

Stomach cancer is a serious threat to global health as it is the world's third leading cause of death from cancer. The major risk behind this disease is that it remains asymptomatic in the early stages. In this study, serum catenin-δ-1 (also known as δ-catenin), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were measured in 70 patients; 20 of which were diagnosed with gastric cancer, 20 with gastric ulcer and 30 with gastritis and also in 20 healthy volunteers as a control group. Infection with Helicobacter pylori was diagnosed by histology, rapid urease test (RUT) and serology, which included IgG and IgA antibodies. The results showed that there was a significant increase in the levels of serum δ-catenin in patients with gastric cancer compared to the control group as well as gastritis and gastric ulcer patients. A significant increase in the levels of δ-catenin was also seen in gastric ulcer and gastritis patients compared to the control group. In addition, a significant increase was seen in δ-catenin serum levels in patients with gastric cancer and gastric ulcer infected with H. pylori compared to the uninfected gastric cancer and gastric ulcer patients. A non-significant increase was observed in the levels of CEA and CA19-9 in all the patients compared to the control group. The results of the present study suggest that serum δ-catenin can serve as a potential marker for gastric cancer.

Full text

CATENIN-δδ
δδ
δ-1 AS A POTENTIAL MARKER OF GASTRIC CANCER IN A
SAMPLE OF IRAQI PATIENTS WITH GASTRIC DISEASES ASSOCIATED
WITH HELICOBACTER PYLORI
Mustafa K. Albayaty1*, Salma A. Abass2, Mohammed F. Al-Marjani3 and Safaa A. A. Razzak4
1Department of Forensic Evidence Techniques, College of Medical Techniques, Al-Farahidi University, Baghdad, Iraq.
2Department of Chemistry, College of Science, Mustansiriyah University, Baghdad, Iraq.
3Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq.
4Gastroenterology and Liver Diseases Hospital, Medical city, Baghdad, Iraq.
*e-mail : mustafa.qahtan@alfarahidiuc.edu.iq
(Received 25 March 2021, Revised 27 April 2021, Accepted 14 May 2021)
ABSTRACT : Stomach cancer is a serious threat to global health as it is the world’s third leading cause of death from cancer.
The major risk behind this disease is that it remains asymptomatic in the early stages. In this study, serum catenin-δδ
δδ
δ-1 (also
known as δδ
δδ
δ-catenin), carcinoembryonic antigen CEA and carbohydrate antigen 19-9 CA 19-9 were measured in 70 patients; 20
of which were diagnosed with gastric cancer, 20 with gastric ulcer and 30 with gastritis and also in 20 healthy volunteers as a
control group. Infection with Helicobacter pylori was diagnosed by histology, rapid urease test (RUT) and serology, which
included IgG and IgA antibodies. The results showed that there was a significant increase in the levels of serum δδ
δδ
δ-catenin in
patients with gastric cancer compared to the control group as well as gastritis and gastric ulcer patients. A significant increase
in the levels of δδ
δδ
δ-catenin was also seen in gastric ulcer and gastritis patients compared to the control group. In addition, a
significant increase was seen in δδ
δδ
δ-catenin serum levels in patients with gastric cancer and gastric ulcer infected with H. pylori
compared to the uninfected gastric cancer and gastric ulcer patients. A non-significant increase was observed in the levels of
CEA and CA 19-9 in all the patients compared to the control group. The results of the present study suggest that serum δδ
δδ
δ-
catenin can serve as a potential marker for gastric cancer.
Key words : δ-catenin, gastric cancer, gastric ulcer, gastritis, Helicobacter pylori.
How to cite : Mustafa K. Albayaty, Salma A. Abass, Mohammed F. Al-Marjani and Safaa A. A. Razzak (2021) Catenin-δ-1 as a
potential marker of gastric cancer in a sample of Iraqi patients with gastric diseases associated with Helicobacter pylori.
Biochem. Cell. Arch. 21, 1949-1954. DocID: https://connectjournals.com/03896.2021.21.1949
INTRODUCTION
Gastric cancer is the world’s third-largest cause of
cancer death and a significant global threat to public
health (Takahiro et al, 2015; Ingrid et al, 2017). More
than 80 percent of the cases are due to H. pylori
infection. Furthermore, gastric carcinogenesis is
contributed also by diet, lifestyle, genetic, social, and other
factors (Magdalena et al, 2017). A very well-established
proposition states that stomach cancer starts the following
infection with H. pylori and proceeds through a stepwise
process of surface-related lesions (superficial then
atrophic gastritis followed by intestinal metaplasia and
dysplasia) (Lydia et al, 2010; Manuel et al, 2015).
The catenin-ä-1 (p120 catenin or ä-catenin) protein
was initially distinguished in a search for Src tyrosine
kinase substrates as a 120 kDa protein. It is externally
like â-catenin, in structure, since it is an individual belonging
to the armadillo (ARM) group of proteins, and also in
functions, since it attaches to cadherins at the AJs (Antonis
et al, 2013). δ-catenin is an auxiliary part of the CCC (E-
Cadherin/β-Catenin/α-Catenin), in addition, it inhibits the
endocytosis of essential cadherins through attachment
with the cytoplasmic juxta-membrane areas of E-cadherin
at a site, which covers their dileucine endocytic motif.
By covering this motif, δ-catenin inhibits the association
between the cytoplasmic tail of traditional cadherins and
Presenilin-1 and Hakai, thus inhibiting the endocytosis of
E-cadherin (Reynolds, 2007). In addition, ä-catenin enrolls
the short finishes of microtubules to the cadherin complex
prompting the development of the junctions. When δ-
catenin dislocates and separates from the complex of E-
cadherin, endocytosis of the membrane E-cadherin occurs
(Davis et al, 2003; Xiao et al, 2003; Hoshino et al, 2005).
Biochem. Cell. Arch. Vol. 21, Supplement 1, pp. 1949-1954, 2021 www.connectjournals.com/bca ISSN 0972-5075
DocID: https://connectjournals.com/03896.2021.21.1949 eISSN 0976-1772

1950 Mustafa K. Albayaty et al
The endocytosed E-cadherins could either be broken down
or reprocessed to the plasma membrane (Hoshino et al,
2005; Balzac et al, 2005). Therefore, δ-catenin is a key
controller, which governs the rebalancing and construction
of E-cadherin into AJs (Stephanie et al, 2016; Qun et al,
2016; Diana et al, 2016; Ji et al, 2016). The dissociation
of ä-catenin from the cadherin-catenin complex, which
occurs during the carcinogenesis process or the damage
done to the cells lining the stomach in cases like gastritis
and gastric ulcer leads to the accumulation of δ-catenin
in the cytoplasm, this dislocated part of the δ-catenin is
believed to leak to the general circulation which enables
its measurement in the blood of the patients. Measurement
of ä-catenin might reflect the status or the integrity of
the cells adhesions in the stomach and thus might be useful
in the diagnosis of gastric cancer. In addition, it might
predict the risk of developing gastric cancer in gastritis
and gastric ulcer patients.
MATERIALS AND METHODS
A total of 70 patients (36 males and 34 females) with
an age range of 18 – 74 and 14 – 85, respectively were
enrolled in this study with (20) healthy individuals (10
males and 10 females) with an age range of 22 – 41 and
18 – 47, respectively serving as the control group. The
patients enrolled in the present study were attending the
educational oncology hospital, medical city, Baghdad, the
endoscopy unit of gastroenterology and liver diseases
hospital, medical city, Baghdad, and the endoscopy unit
of Azadi Teaching Hospital, Duhok. This study was
approved by the Department of Chemistry, College of
Science, Al-Mustansiriyah University, Baghdad, Iraq, the
Iraqi Ministry of Health, and by the Research Ethics
Committee of Duhok Directorate General of Health,
Kurdistan Regional Government, Iraq. The study subjects
were divided into (3) groups according to their clinical
diagnosis; (20) patients with gastric cancer (12 males
and 8 females) with an age range of (37 – 74 and 59 – 85
respectively). (20) patients with gastric ulcer (10 males
and 10 females) with an age range of (19 – 60 and 14 –
60 respectively). (30) patients with gastritis (14 males
and 16 females) with an age range of (18 – 55 and 17 –
40 respectively).
Exclusion criteria
Cases were excluded from this study if one or more
of the following criteria were present; current or previous
chemotherapy, current or previous antibiotic or PPI
treatment, use of NSAID drugs, the presence of another
type of cancer, the presence of liver inflammation, or
other related liver diseases, gastrectomy and H. Pylori
infected volunteers.
Samples collection
Ten milliliters of blood were collected from each
patient and healthy control. Blood samples were
transferred into gel tubes and left for 15 – 30 minutes at
room temperature to clot. The blood samples were then
centrifuged and the obtained serum samples were stored
at -20ºC till assayed. In addition, biopsy samples were
also collected from the stomach of the patients by the
physicians performing the endoscopy for histology and
RUTs.
Histology and rapid urease test (RUT)
Histology was performed by specialized histologists
in the laboratories of each hospital from which the
biopsies were taken. RUT was performed in the
endoscopy unit during the endoscopy procedure. A biopsy
from the antrum was combined with a biopsy from the
corpus and was placed on the RUT cassette and covered.
After one hour, a color change (from yellow to pink)
indicated a positive test.
Biochemical analyses
Serum δ-catenin was measured by enzyme-linked
immunosorbent assay (ELISA) using the Human δ-
catenin Elisa Kit provided by (Shanghai Biological /
China) following the manufacturer’s directions. Anti-H.
pylori IgG and IgA antibodies were measures by (ELISA)
using Helicobacter IgG Elisa Kit and Helicobacter IgA
Elisa Kit provided by (Demeditec/ Germany) following
the manufacturer’s directions. CEA and CA 19-9 tumor
markers were measured by enzyme-linked fluorescent
assay (ELFA) using VIDAS CEA (S) and VIDAS CA
19-9 (199) kits provided by (Biomerieux/ France)
following the manufacturer’s directions.
Statistical analyses
Biochemical data were analyzed using SPSS
(statistical package for social sciences) version 25. T-
Test was used to calculate the mean ± standard deviation
(SD) and the p-value.
RESULTS AND DISCUSSION
Diagnosis of H. pylori infection
The infection with H. pylori was diagnosed by
histology, RUT, IgA and IgG antibodies. Fifty (71.43%)
out of the seventy patients were positive for H. pylori
while all the healthy controls were negative for the
infection. Patients were considered positive if at least
two of the mentioned tests were positive. Tables 1 and 2
shows the status of the infection of each group in this
study and the results of each diagnostic method compared
with the others, respectively.

Catenin-δ-1 as a potential marker of gastric cancer in a sample of Iraqi patients 1951
Fifty patients (71.4%) were proved to be positive for
H. pylori infection by histology and RUT and as such,
they were considered to have a sensitivity and specificity
of (100 %). Histology was the first method to be used to
diagnose H. pylori and is considered the standard gold
method (Farzaneh et al, 2016; Ana et al, 2014). The RUT
operates on the principle that H. pylori produce huge
amounts of the urease enzyme that hydrolyses the host
urea producing ammonia, which can be detected by a
variety of indirect means (Choi et al, 2012; Moon et al,
2012). However, many factors affect histology and RUT
accuracy as diagnostic methods, such as size, the number
of biopsies, site of biopsies and methods of staining, proton
pump inhibitor (PPI), antibiotics, and the pathologist’s
experience, time-consuming, relatively costly, bleeding
(such as bleedings of peptic ulcers) (Ana et al, 2014),
gastrectomy (Tian et al, 2012; Yao-Kuang et al, 2015;
Saurabh et al, 2014; Amin, 2018). Several studies
concluded that, in addition to increasing the number of
biopsies, the collection of biopsies from different regions
of the stomach could result in a higher accuracy of RUT
(Farzaneh et al, 2016; Yao-Kuang et al, 2015; Amin,
2018). The low diagnosis cost, ease, and speed give the
RUT the upper hand over histology.
Fifty-nine patients (84.3%) were positive for the anti-
H. pylori IgG antibodies, while only eleven patients
(15.7%) were positive for the anti-H. pylori IgA
antibodies. The results of IgG showed only nine false-
positive cases and zero false-negative cases. In contrast,
IgA results showed thirty-nine false-negative cases and
zero false-positive cases. Accordingly, we concluded that
IgG showed better results in terms of sensitivity and
overall diagnostic accuracy. IgA results turned to be less
trustful and less reliable. Studies also showed that IgA
based serologic tests were much less useful and less
accurate in contrast to IgG based tests which showed
sensitivities up to (100%) and specificities of (58 – 97%)
supporting that IgG tests are more accurate and reliable
(Rosemary et al, 2009; Babak et al, 2013; Julian et al,
1990). High levels of IgG are seen in nearly all individuals
with H. pylori infection, but IgA levels exceed cut-off
values in only about two-thirds of cases (Pandya et al,
2014). Serological tests are generally relatively cheap,
performed quickly and, unlike invasive methods, cause
minimal discomfort to the patient (Priya et al, 2017).
Diagnosis of H. pylori with serology is not influenced by
gastric atrophy, ulcer bleedings, or PPI and antibiotics
(Yao-Kuang et al, 2015; Amin, 2018). Still, these tests
are not useful in evaluating eradication therapy because,
even after complete eradication, antibody levels remain
in the blood for extended periods (Yoshihisa et al, 2004).
These tests cannot differentiate active (current) infection
from past (inactive) infection, which makes these tests
unreliable in solely diagnosing H. pylori (Priya et al, 2017;
Best et al, 2018).
Serum levels of δδ
δδ
δ-catenin, CEA and CA 19-9
A significant increase in the levels of ä-catenin was
observed in the sera of patients diagnosed with gastric
ulcer (20.31 ± 0.94351) and gastritis (17.07 ± 0.8799)
compared to the control group (14.03 ± 1.47) (p < 0.001),
there was also a significant increase in the levels of δ-
catenin in sera of gastric cancer patients (28.34 ±
3.956823) in comparison to the controls as well as to the
gastric ulcer and gastritis groups. There was a small,
statistically non-significant increase in the levels of CEA
in the sera of gastric cancer patients (3.96 ± 1.93)
compared to the control group (2.98 ± 1.41) (p = 0.094)
as well as to the gastric ulcer (3.77 ± 1.64) and gastritis
patients (3.62 ± 1.42). A non-significant increase was
also seen in the levels of CA 19-9 in sera of patients
diagnosed with gastric cancer (17.68 ± 17.04) compared
to the control group (13.03 ± 8.35) (p = 0.313) as well as
to gastric ulcer (14.40 ± 9.13) and gastritis patients (13.94
± 7.74). Tables 3 and 4 shows the levels of ä-catenin,
CEA and CA 19-9 in patients’ groups and controls.
There was a large significant increase in the levels
of ä-catenin in sera of gastric cancer patients infected
Table 1 : Helicobacter pylori status of patients and control groups.
Groups H. pylori H. pylori
Positive Negative
N (%) N (%)
Gastric cancer 7 (35) 13 (65)
Total N = 20
Gastric ulcer 13 (65) 7 (35)
Total N = 20
Gastritis 30 (100) 0 (0)
Total N = 30
Control 0 (0) 20 (100)
Total N = 20
Table 2 : Results of Helicobacter pylori diagnostic methods.
Diagnostic method Positive cases Negative cases
N (%) N (%)
Patients N = 70 50 (71.4) 20 (28.6)
Histology 50 (71.4) 20 (28.6)
RUT 50 (71.4) 20 (28.6)
IgG 59 (84.3) 11 (15.7)
IgA 11 (15.7) 59 (84.3)
Control N = 20 0 (0) 20 (100)
IgG 0 (0) 20 (100)
IgA 0 (0) 20 (100)

1952 Mustafa K. Albayaty et al
with H. pylori (32.50 ± 0.99) compared to uninfected
gastric cancer patients (26.09 ± 3.03). There was also a
significant increase in ä-catenin levels in the sera of gastric
ulcer patients infected with H. pylori (20.91 ± 0.50)
compared to uninfected gastric ulcer patients (19.19 ±
0.37). There were no significant differences in the levels
of CEA and CA 19-9 tumor markers between H. pylori-
infected and H. pylori uninfected patients.
The significant segments of the adherens junctions
(AJs) proteins are E-Cadherin, β-Catenin and Catenin-
δ-1 (also known as p120 catenin). The AJs are confined
beneath the tight intersections (junctions) (TJs) and
playout numerous roles including stabilizing cell-cell
attachment, starting TJs gathering, adjusting cytoskeleton
modification, transcriptional regulation, and signaling
transduction Epithelial cells’ AJs contribute to maintaining
epithelial barrier integrity and loss of the AJs integrity
has been connected to tumor initiation and progression
(Junting et al, 2018). In the present study, all the study
subjects suffer from defects or damage in the cells lining
the stomach and these defects extend over different
degrees depending on the condition. Such defects are
thought to influence the cells’ adhesion and as such the
AJs complex. Furthermore, H. pylori stimulating the
proteolytic cleavage of the E-Cadherin extracellular
domain (David et al, 2012; Sandra et al, 2017). This
cleavage leads to the disassembly of the adheres junctions
complex and the subsequent accumulation of the β-
catenin and catenin-δ-1 in the cytoplasm (Nelson et al,
2004; Backert et al, 2017). This accumulated ä-catenin
might leak into the general circulation, which enables its
determination in the blood of the patients. This might give
a possible explanation for the findings of the current study
and might further explain the increased levels of this
protein in the patients infected with H. pylori, this also
may represent one of the possible mechanisms for the
influence of H. pylori on the pathogenesis of gastric
diseases. Based on these findings, elevated levels of δ-
catenin can be employed in the diagnosis of gastric cancer.
The elevated levels of ä-catenin in gastritis and gastric
ulcer patients might indicate the tendency and the possible
risk of developing gastric cancer in these patients.
Through intensive search in the literature, we could not
find a single study regarding serum levels of catenin-δ-1
in any diseases or disorders and this research would
represent the first study to describe its role in gastric-
related diseases.
The majority of studies demonstrate that CEA and
CA 19-9 markers are advantageous tools for metastasis
and recurrence of malignancies as well as for assessing
the effectiveness of chemotherapy and prognosis in
gastric malignant growth (Wang et al, 2014; Jing et al,
2013). However, CA 19-9 and CEA are not helpful for
the finding of early gastric malignancy (Feng et al, 2017).
Elevated concentrations of these markers are also seen
in different tumors and some nonmalignant conditions,
for example, gastritis, gastric ulcer, duodenitis, and
esophagitis (Ozgur, 2015; Xin et al, 2010; Cãtãlina et al,
2016). The consequences of certain investigations
question the advantage of CA 19-9 and CEA even as
monitoring or observing markers in gastric cancers (Polat
et al, 2014; Ohtsuka et al, 2008; Hasbahceci et al, 2018;
Junxiu et al, 2016). The results of the present study are
in accordance with the previous studies, the tumor
Table 3 : Levels of serum Catenin-ä-1, CEA and CA 19-9 in patients and control groups.
Parameters Gastric Cancer Gastric Ulcer Gastritis Control p-value p-value p-value
(A) (B) (C) (D) A vs D B vs D C vs D
Mean ± SD Mean ± SD Mean ± SD Mean ± SD
Catenin-ä-1 28.34 ± 3.956823 20.31 ± 0.94351 17.07 ± 0.8799 14.03 ± 1.47 0.000* 0.000* 0.000*
(ng/mL)
CEA (ng/mL) 3.96 ± 1.93 3.77 ± 1.64 3.62 ± 1.42 2.98 ± 1.41 0.094 0.135 0.147
CA 19-9 (U/mL) 17.68 ± 17.04 14.40 ± 9.13 13.94 ± 7.74 13.03 ± 8.35 0.313 0.642 0.708
*Significant at the level of (0.05).
Table 4 : Levels of serum Catenin-ä-1, CEA and CA 19-9 in patients’ groups.
Parameters Gastric Cancer Gastric Ulcer Gastritis p-value p-value p-value
(A) (B) (C) A vs B A vs C B vs C
Mean ± SD Mean ± SD Mean ± SD
Catenin-ä-1 28.34 ± 3.956823 20.31 ± 0.94351 17.07 ± 0.8799 0.000* 0.000* 0.000*
(ng/mL)
CEA (ng/mL) 3.96 ± 1.93 3.77 ± 1.64 3.62 ± 1.42 0.743 0.484 0.740
CA 19-9 (U/mL) 17.68 ± 17.04 14.40 ± 9.13 13.94 ± 7.74 0.464 0.308 0.852
*Significant at the level of (0.05).

Catenin-δ-1 as a potential marker of gastric cancer in a sample of Iraqi patients 1953
markers in this research were not useful nor reliable in
the diagnosis of gastric cancer.
CONCLUSION
Catenin-δ-1 may serve as a potential marker for the
diagnosis of gastric cancer and it may also serve as a
possible risk predictor for the development of gastric
cancer in gastritis and gastric ulcer patients. CEA and
CA 19-9 tumor markers are not adequate and reliable
tools for the diagnosis of gastric cancer. H. pylori
contribute to the damage of the adheren junctions that
link the stomach cells with each other.
ACKNOWLEDGEMENT
This work was supported by the Department of
Chemistry and the Department of Biology, College of
Science at Mustansiriyah University, Baghdad, Iraq.
REFERENCES
Amin T B (2018) Diagnosis of Helicobacter pylori Using Invasive and
Noninvasive Approaches. Hindawi J. Pathogens 2018, Article
ID 9064952, 13 pages https://doi.org/10.1155/2018/9064952
Ana I L, Filipa F V and Mónica O (2014) Helicobacter pylori infection
- recent developments in diagnosis. World J Gastroenterol.
20(28), 9299 – 9313.
Antonis K, Siu P N and Panos Z A (2013) p120 catenin: an essential
regulator of cadherin stability, adhesion-induced signaling, and
cancer progression. Prog. Mol. Biol. Transl. Sci. 116, 409–432.
Babak P, Mona G, Shima M, Setareh M, Hossein A, Mehri N, Bahram
K, Ali S and Akbar M (2013) Diagnosis of Helicobacter pylori
infection by invasive and noninvasive tests. Braz. J. Microbiol.
44(3), 795-798.
Backert S, Schmidt T P, Harrer A and Wessler S (2017) Exploiting the
Gastric Epithelial Barrier: Helicobacter pylori’s Attack on Tight
and Adherens Junctions. Curr Top Microbiol Immunol. 400,
195-226.
Balzac F, Avolio M, Degani S, Kaverina I, Torti M, Silengo L, Small J
V and Retta S F (2005) E-cadherin endocytosis regulates the
activity of Rap1: a traffic light GTPase at the crossroads between
cadherin and integrin function. J. Cell Sci. 118(20), 4765–4783.
Best L M, Takwoingi Y, Siddique S, Selladurai A, Gandhi A, Low
B, Yaghoobi M and Gurusamy K S (2018) Non-invasive
diagnostic tests for Helicobacter pylori infection. Cochrane
Database Syst. Rev. 15(3), 1 – 327.
Cãtãlina D, Mãdãlina I, Gaudia M A, Laura V, Daniel O C and Raluca
S C (2016) Tumor markers in gastroenterology: useful or useless.
Romanian J. Military Med. 119(2), 17 – 22.
Choi Y J, Kim N, Lim J, Jo S Y, Shin C M, Lee H S, Lee S H, Park Y
S, Hwang J H, Kim J W, Jeong S H, Lee D H and Jung H C
(2012) Accuracy of diagnostic tests for Helicobacter pylori in
patients with peptic ulcer bleeding. Helicobacter 17, 77 – 85.
David J M and Rajasekaran A K (2012) Dishonorable discharge: the
oncogenic roles of cleaved E-cadherin fragments. Cancer Res.
72(12), 2917–2923.
Davis M A, Ireton R C and Reynolds A B (2003) A core function for
p120-catenin in cadherin turnover. J. Cell Biol. 163(3), 525–
534.
Diana P W, Fernando C, Ana E G, Angela G, Juan M L and Carlos O
A (2016) P120-Catenin Regulates Early Trafficking Stages of
the N-Cadherin Precursor Complex. PLoS One 11(6), 1 – 21.
Farzaneh J, Safar F, Mohammad H S, Zoya H, Rana Y and Nazli S
(2016) Comparative Evaluation of RUT, PCR and ELISA Tests
for Detection of Infection with Cytotoxigenic H. pylori. Adv.
Pharm. Bull. 6(2), 261-266.
Feng F, Tian Y, Xu G, Liu Z, Liu S, Zheng G, Guo M, Lian X, Fan D
and Zhang H (2017) Diagnostic and prognostic value of CEA,
CA19-9, AFP and CA125 for early gastric cancer. BMC Cancer
17(1), 737 – 743.
Hasbahceci M, Malya F U, Kunduz E, Guler M, Unver N and
Akcakaya A (2018) Use of serum and peritoneal CEA and CA19-
9 in the prediction of peritoneal dissemination and survival of
gastric adenocarcinoma patients: are they prognostic factors?
Ann. R. Coll. Surg. Engl. 100(4), 257–266.
Hoshino T, Sakisaka T, Baba T, Yamada T, Kimura T and Takai Y
(2005) Regulation of E-cadherin endocytosis by nectin through
afadin, Rap1 and p120ctn. J. Biol Chem. 280(25), 24095–24103.
Ingrid P V, Rachel S V, Han J V, Liesbeth S, Wendy A Z and Marleen K
(2017) Unraveling genetic predisposition to familial or early-
onset gastric cancer using germline whole-exome sequencing.
Europ. J. Human Genetics 25(11), 1246–1252.
Ji Y H, Il-Hoan O and Pierre D M (2016) Phosphorylation and isoform
use in p120-catenin during development and tumorigenesis.
Biochim. Biophys. Acta 1863(1), 102–114.
Jing J, Xu X, Du L, Tian B, Sun T, Zhao X and Han C (2013) Clinical
assessment and prognostic evaluation of tumor markers in
patients with gastric cancer. Int. J. Biol. Markers 28, 192–200.
Julian E T, Adrian M W, Michael R B, Ed J E and Michael A K (1990)
Serodiagnosis of Helicobacter pylori Infection in Childhood. J.
Clin. Microbiol. 28(12), 2641-2646.
Junting C, Miranda K C, Yutong Z and Jing Z (2018) The role of
ubiquitination and deubiquitination in the regulation of cell
junctions. Protein Cell 9(9),754–769.
Junxiu Y, Shuguang Z and Bingbo Z (2016) Differences and correlation
of serum CEA, CA19-9 and CA72-4 in gastric cancer. Mole.
Clin. Oncol. 4(3), 441-449.
Table 5 : Levels of serum Catenin-ä-1, CEA and CA 19-9 in H. Pylori infected patients.
Gastric Cancer (Mean ± SD) Gastric Ulcer (Mean ± SD)
Parameters p-value p-value
HP + HP - HP + HP -
Catenin-ä-1 (ng/mL) 32.50 ± 0.99 26.09 ± 3.03 0.000* 20.91 ± 0.50 19.19 ± 0.37 0.000*
CEA (ng/mL) 3.90 ± 1.02 3.99 ± 2.27 0.929 3.56 ± 1.18 4.15 ± 2.21 0.472
CA 19-9 (U/mL) 16.66 ± 11.73 18.14 ± 19.29 0.853 14.56 ± 9.45 14.07 ± 8.49 0.912
HP: H. pylori. *Significant at the level of (0.05).

1954 Mustafa K. Albayaty et al
Lydia E W, Richard M P and Keith T W (2010) Helicobacter pylori
and Gastric Cancer: Factors That Modulate Disease Risk. Clin.
Microbiol. Reviews 23(4), 713–739.
Magdalena C, Zuzanna K, Weronika G, Bujana A and Pawe³ S (2017)
Host pathogen interactions in Helicobacter pylori related gastric
cancer. World J. Gastroenterol. 23(9), 1521-1540.
Manuel A V, Jimena C, Alejandro H C and Andrew F Q (2015)
Helicobacter pylori -induced inflammation and epigenetic changes
during gastric carcinogenesis. World J. Gastroenterol. 21(45),
12742-12756.
Moon S W, Kim T H, Kim H S, Ju J H, Ahn Y J, Jang H J, Shim S G,
Kim H J, Jung W T and Lee O J (2012) United Rapid Urease
Test Is Superior than Separate Test in Detecting Helicobacter
pylori at the Gastric Antrum and Body Specimens. Clin. Endosc.
45, 392 – 396.
Nelson W J and Nusse R (2004) Convergence of Wnt, beta-catenin,
and cadherin pathways. Science 303(5663), 1483–14877.
Ohtsuka T, Sato S, Kitajima Y, Tanaka M, Nakafusa Y and Miyazaki
K (2008) False-positive findings for tumor markers after curative
gastrectomy for gastric cancer. Dig. Dis. Sci. 53, 73–79.
Ozgur T (2015) The diagnostic value of tumor markers and endoscopy
in patients with gastric disorders. Arch. Clin. and Exp. Surg.
4(2), 74-78.
Pandya H B, Patel J S, Agravat H H and Singh N K (2014) Non-
Invasive Diagnosis of Helicobacter pylori: Evaluation of Two
Enzyme Immunoassays, Testing Serum IgG and IgA Response
in the Anand District of Central Gujarat, India. J. Clin. Diagn.
Res. 8(6), 12-17.
Polat E, Duman U, Duman M, Derya P K, Akyuz C, Fatih Y N, Uzun
O, Akbulut S, Birol B E and Yol S (2014) Preoperative serum
tumor marker levels in gastric cancer. Pak. J. Med. Sci. 30, 145–
149.
Priya R, John F T and Debra H P (2017) Helicobacter pylori serology
testing is a useful diagnostic screening tool for symptomatic
inner city children. Acta Paediatr. 106(3), 470–477.
Qun L, Byron J A, Mingchuan L, Yongguang J and Yan-Hua C (2016)
Genetic Alterations of ä-Catenin/NPRAP/Neurojungin
(CTNND2): Functional Implications in complex human diseases.
Hum. Genet. 135(10), 1107–1116.
Reynolds A B (2007) p120-catenin: Past and present. Biochim. Biophys.
Acta 1773(1), 2–7.
Rosemary C S, Andrew R W and Christine M L (2009) Evaluation of
Helicobacter pylori Immunoglobulin G (IgG), IgA and IgM
Serologic Testing Compared to Stool Antigen Testing. Clin.
Vaccine Immunol. 16(8), 1253–1255.
Sandra L V, Juan-Jose S A, Ana-Lourdes Z P, Blanca-Patricia L R,
Margarita-Delaluz M F, Rogelio G G, Nelly M F, Mario-Alberto
I E and Ronell B M (2017) Patients with advanced oral squamous
cell carcinoma have high levels of soluble E-cadherin in the saliva.
Med. Oral Patol. Oral Cir. Bucal. 22(6), 694 – 701.
Saurabh K P, Chandra B P, Ashok K J, Anil K G and Gopal N (2014)
Diagnosis of Helicobacter pylori: What should be the gold
standard. World J. Gastroenterol. 20(36), 12847-12859.
Stephanie L M, Yuliya I P and Barry M G (2016) Microtubules Inhibit
E-Cadherin Adhesive Activity by Maintaining Phosphorylated
p120-Catenin in a Colon Carcinoma Cell Model. PLoS One
11(2), 1 – 18.
Takahiro S, Hiroyuki M, Norihiko W and Tsutomu C (2015) Molecular
Pathogenesis of Helicobacter pylori-Related Gastric Cancer.
Gastroenterol. Clin. North Am. 44(3), 625-638.
Tian X Y, Zhu H, Zhao J, She Q and Zhang G X (2012) Diagnostic
performance of urea breath test, rapid urea test, and histology
for Helicobacter pylori infection in patients with partial
gastrectomy: a meta-analysis. J. Clin. Gastroenterol. 46, 285-
292.
Wang Q, Yang Y, Zhang Y P, Zou Z, Qian X, Liu B and Wei J (2014)
Prognostic value of carbohydrate tumor markers and
inflammation-based markers in metastatic or recurrent gastric
cancer. Med. Oncol. 31, 289.
Xiao K, Allison D F, Buckley K M, Kottke M D, Vincent P A,
Faundez V and Kowalczyk A P (2003) Cellular levels of p120
catenin function as a set point for cadherin expression levels in
microvascular endothelial cells. J. Cell Biol. 163(3), 535–545.
Xin A, Pei-Rong D, Xiao-Juan X, Zhi-Qiang W, Feng-Hua W, Fen F,
Wen-Qi J, You-Jian H, Rui-Hua X and Yu-Hong L (2010)
Carcinoembryonic antigen surge in metastatic Colorectal cancer
patients responding to irinotecan combination chemotherapy.
Biomarkers 15(3), 243–248.
Yao-Kuang W, Fu-Chen K, Chung-Jung L, Meng-Chieh W, Hsiang-
Yao S, Sophie S W, Jeng-Yih W, Chao-Hung K, Yao-Kang H and
Deng-Chyang W (2015) Diagnosis of Helicobacter pylori
infection: Current options and developments. World J.
Gastroenterol. 21(40), 11221-11235.
Yoshihisa U, Kazuo H, Naotaka T, Yoshinori K, Hidenori K, Eiko K,
Masahiko S and Kazumasa M (2004) Comparison of serum IgA
and IgG antibodies for detecting Helicobacter pylori infection.
Internal Medicine 43(7), 548 – 552.