Vascular endothelial growth factor (VEGF) serum levelsof patients with Helicobacter pylori gastritis with cytotoxin-associated gene A positive (CagA+)status

https://doi.org/10.19106/JMedSci005104201907

Wira Prihatin Siregar(1*), Gontar Alamsyah Siregar(2), Taufik Sungkar(3)

(1) Gastroentero-hepatology Division of Internal Medicine Department, Medical Faculty of University of Sumatera Utara / Haji Adam Malik General Hospital
(2) Gastroentero-hepatology Division of Internal Medicine Department, Medical Faculty of University of Sumatera Utara / Haji Adam Malik General Hospital
(3) Gastroentero-hepatology Division of Internal Medicine Department, Medical Faculty of University of Sumatera Utara / Haji Adam Malik General Hospital
(*) Corresponding Author

Abstract


Helicobacter pylori (H.pylori) is an agent that causes gastritis and the ulcer of gaster, which are ultimately caused gastric tumors. The prevalence is about 80 % average in developing country and 20-50 % in developed countries. One of the virulence factor iscytotoxin-associated gene A (CagA) that plays a role in the inflammation process,cell proliferation and metaplasia in gastric mucosa. Vascular endothelial growth factor (VEGF)is one of angiogenic factors that plays a role in the process of making new mucosal tissue after the inflammation by H.pylori. The escalation of VEGF expression levels contribute to the beginning of gastric carcinogenesis. The studywas aimed to analyze of VEGF serum levels between CagA(+) and CagA(-) in patients with H.pylori gastritis. Cross sectional study was conducted on 30 patients with H.pylori gastritis after conducted gastroscopy,biopsy and CLO test, which were continued with VEGF serum examination using ELISA test and perfomed PCR test to determinethe CagA status.The data was analyzed with SPSS 22 version andp value <0.05 was considered significant.The results of this study were18 men (60 %) and 12 women (46%) from 30 total subjects, with a median age average was 53.5 years old.Majority ethnic was Batak with 16 subjects (53.3%). Helicobacterpylori gastritis with CagA(+) was about 21 subjects (70%) and H.pylori gastritis with CagA(-) was about 9 subjects (30%). We found that median VEGF serum levels of patients with H.pylori gastritis with CagA(+)[480.3 pg/dL (115.5-2185.2)] significantly higher compared to thatwith CagA(-) [291.1 pg/dL (158.4-556.7)] (p<0.05).In conclusion, the VEGF serum levels ofpatients withH.pylori gastritis with CagA(+) is higher compared to that withCagA(-).


Keywords


Gastritis, H.pylori, CagA, VEGF, gastric tumor

Full Text:

PDF


References

1. Rugge M,Genta RM. Staging and grading of chronic gastritis. Hum pathol 2005; 36(3):228-33.
https://doi.org/10.1016/j.humpath.2004.12.008
2. Fox JG, Megraud F. Helicobacter. In: Murray PR, editor. Manual of clinical microbiology. 9th ed. Pensylvania: Elsevier Mosby; 2007: 947-62.
3. Cesar ACG, Cury PM, Payao SLM, Liberatore PR, Silva AE. Comparison of histological and molecular diagnosis of Helicobacter pylori in benign lesions and gastric adenocarcinoma. Braz J Microbiol 2005; 36(1):12-16.
https://doi.org/10.1590/S1517-83822005000100003
4. Banerjee A, Mukhopadhyay AK, Paul S, Bhattacharyya A, Swarnakar S. Unveiling the intricacies of Helicobacter pylori-induced gastric inflammation: T helper cells and matrix metalloproteinases at a crossroad. In Mozsik G, editor. Current Topics in Gastritis. Croatia: InTech Publishers; 2013.Chapter 7.
https://doi.org/10.5772/54193
5. Maciorkowska E, Marcinkiewicz S, Kaczmarski M, Kemona A. Inflammatory changes of the gastric mucosa and serum concentration of chosen growth factors in children. Adv Med Sci 2010; 55(1):59-66.
https://dx.doi.org/10.2478/v10039-010-0007-6
6. Aziz F,Chen X,Yang X, Yan Q.Prevalence and correlation with clinical diseases of helicobacter pylori caga and vaca genotype among gastric patients from northeast China.BioMed Research International 2014; 2014:1-7.
https:/doi.org/10.1155/2014/142980
7. Tahara T, Arisawa T, Shibata T, Nakamura M, Yamashita H, Yoshioka D, et al. Effect of polymorphisms in the 3’-untranslated region (3’-UTR) of VEGF gene on gastric premalignant condition. Anticancer Res 2009; 29(2):485-9.
8. Matsukura N, Yamada S, Kato S, Tomtitchong P, Tajiri T, Miki M, et al. Genetic differences in interleukin-1 betapolymorphisms among four Asian populations: an analysis of the Asian paradox between H. pylori infection and gastric cancer incidence. J Exp Clin Cancer Res 2003; 22 (1):47-55.
9. Caputo R, Tuccillo C, Manzo BA, Zarrilli R, Tortora G, Blanco CV, et al. Helicobacter pylori VacA toxin up-regulates vascular endothelial growth factor expression in MKN 28 gastric cells through an epidermal growth factor receptor-, cyclooxygenase-2-dependent mechanism. Clin Cancer Res 2003;9(6):2015-21.
10. Jamaludin,Siregar GA. Perbandingan kadar serum VEGF dan MMP 9 pada pasien gastritis H.Pylori dan Non-H.Pylori.[Thesis], Magister Program Studi Ilmu Penyakit Dalam Fakultas Kedokteran USU.2015.
Site: http://www.repository.usu.ac.id.
11. Zhu Y, Zhou X, Wu J, Su J, Zhang G. Risk factors and prevalence of H.Pylori infection in persistent high incidence area of gastric carcinoma in Yangzhong city.Gastroenterol Res Pract2014; 2014:481365.
https://doi.org/10.1155/2014/481365
12. Betty, Lubis CP, Siregar GA. Infeksi Helicobacter pylori pada lesi gastritis yang didiagnosa dengan pewarnaan histokimia giemsa dan imunohistokimia Helicobacter pyloridi Laboratorium Patologi Anatomi Fakultas Kedokteran USU Medan.[Thesis].Fakultas Kedokteran USU,2012.
http://repository.usu.ac.id/handle/123456789/34694.
13. Churin Y, Laila AG, Oliver K, Thomas FM, Walter B, Michael N.Helicobacter pylori Cag A protein targets the c-Met receptor and enhances the motogenic response. JCell Biol2003;161(2):249-55.
https://doi.org/10.1083/jcb.200208039
14. Karayiannakis AJ, Syrigos KN, Polychronidis A, Zbar A, Kouraklis G, Simopoulos C, et al. Circulating VEGF levels in the serum of gastric cancer patients correlation with pathological variables, patient survival, and tumor surgery. Ann Surg2002; 236(1):37-42.
https://doi.org/10.1097/00000658-200207000-00007
15. Mangia A,Chiriatti A, Ranieri G, Abbate I, Coviello M, Simone G, etal.H.Pylori status and angiogenesis factor in human gastric carcinoma.World J Gastroenterol2006; 12(34):5465-72.
https://doi.org/10.3748/wjg.v12.i34.5465

1. Rugge M,Genta RM. Staging and grading of chronic gastritis. Hum pathol 2005;36(3):228-33.

https://doi.org/10.1016/j.humpath.2004.12.008

2. Fox JG, Megraud F. Helicobacter. In: Murray PR, editor. Manual of clinical microbiology. 9th ed. Pensylvania: Elsevier Mosby; 2007: 947-62.

3. Cesar ACG, Cury PM, Payao SLM, Liberatore PR, Silva AE. Comparison of histological and molecular diagnosis of Helicobacter pylori in benign lesions and gastric adenocarcinoma. Braz J Microbiol 2005;36(1):12-16.

https://doi.org/10.1590/S1517-83822005000100003

4. Banerjee A, Mukhopadhyay AK, Paul S, Bhattacharyya A, Swarnakar S. Unveiling the intricacies of Helicobacter pylori-induced gastric inflammation: T helper cells and matrix metalloproteinases at a crossroad. In Mozsik G, editor. Current Topics in Gastritis. Croatia: InTech Publishers; 2013.Chapter 7.

https://doi.org/10.5772/54193

5. Maciorkowska E, Marcinkiewicz S, Kaczmarski M, Kemona A. Inflammatory changes of the gastric mucosa and serum concentration of chosen growth factors in children. Adv Med Sci 2010; 55(1):59-66.

https://dx.doi.org/10.2478/v10039-010-0007-6

6. Aziz F,Chen X,Yang X, Yan Q.Prevalence and correlation with clinical diseases of helicobacter pylori caga and vaca genotype among gastric patients from northeast China.BioMed Research International 2014; 2014:1-7.

https:/doi.org/10.1155/2014/142980

7. Tahara T, Arisawa T, Shibata T, Nakamura M, Yamashita H, Yoshioka D, et al. Effect of polymorphisms in the 3’-untranslated region (3’-UTR) of VEGF gene on gastric premalignant condition. Anticancer Res 2009; 29(2):485-9.

8. Matsukura N, Yamada S, Kato S, Tomtitchong P, Tajiri T, Miki M, et al. Genetic differences in interleukin-1 betapolymorphisms among four Asian populations: an analysis of the Asian paradox between H. pylori infection and gastric cancer incidence. J Exp Clin Cancer Res 2003; 22 (1):47-55.

9. Caputo R, Tuccillo C, Manzo BA, Zarrilli R, Tortora G, Blanco CV, et al. Helicobacter pylori VacA toxin up-regulates vascular endothelial growth factor expression in MKN 28 gastric cells through an epidermal growth factor receptor-, cyclooxygenase-2-dependent mechanism. Clin Cancer Res 2003;9(6):2015-21.

10.Jamaludin,Siregar GA. Perbandingan kadar serum VEGF dan MMP 9 pada pasien gastritis H.Pylori dan Non-H.Pylori.[Thesis], Magister Program Studi Ilmu Penyakit Dalam Fakultas Kedokteran USU.2015.

Site: http://www.repository.usu.ac.id.

11.Zhu Y, Zhou X, Wu J, Su J, Zhang G. Risk factors and prevalence of H.Pylori infection in persistent high incidence area of gastric carcinoma in Yangzhong city.Gastroenterol Res Pract2014; 2014:481365.

https://doi.org/10.1155/2014/481365

12.Betty, Lubis CP, Siregar GA. Infeksi Helicobacter pylori pada lesi gastritis yang didiagnosa dengan pewarnaan histokimia giemsa dan imunohistokimia Helicobacter pyloridi Laboratorium Patologi Anatomi Fakultas Kedokteran USU Medan.[Thesis].Fakultas Kedokteran USU,2012.

http://repository.usu.ac.id/handle/123456789/34694.

13.Churin Y, Laila AG, Oliver K, Thomas FM, Walter B, Michael N.Helicobacter pylori Cag A protein targets the c-Met receptor and enhances the motogenic response. JCell Biol2003;161(2):249-55.

https://doi.org/10.1083/jcb.200208039

14.Karayiannakis AJ, Syrigos KN, Polychronidis A, Zbar A, Kouraklis G, Simopoulos C, et al. Circulating VEGF levels in the serum of gastric cancer patients correlation with pathological variables, patient survival, and tumor surgery. Ann Surg2002; 236(1):37-42.

https://doi.org/10.1097/00000658-200207000-00007

15.Mangia A,Chiriatti A, Ranieri G, Abbate I, Coviello M, Simone G, etal.H.Pylori status and angiogenesis factor in human gastric carcinoma.World J Gastroenterol2006; 12(34):5465-72.

https://doi.org/10.3748/wjg.v12.i34.5465

Normal

0

false

false

false

EN-US

X-NONE

X-NONE

DefSemiHidden="false" DefQFormat="false" DefPriority="99"

LatentStyleCount="371">

UnhideWhenUsed="true" QFormat="true" Name="heading 2"/>

UnhideWhenUsed="true" QFormat="true" Name="heading 3"/>

UnhideWhenUsed="true" QFormat="true" Name="heading 4"/>

UnhideWhenUsed="true" QFormat="true" Name="heading 5"/>

UnhideWhenUsed="true" QFormat="true" Name="heading 6"/>

UnhideWhenUsed="true" QFormat="true" Name="heading 7"/>

UnhideWhenUsed="true" QFormat="true" Name="heading 8"/>

UnhideWhenUsed="true" QFormat="true" Name="heading 9"/>

Name="index 1"/>

Name="index 2"/>

Name="index 3"/>

Name="index 4"/>

Name="index 5"/>

Name="index 6"/>

Name="index 7"/>

Name="index 8"/>

Name="index 9"/>

UnhideWhenUsed="true" Name="toc 1"/>

UnhideWhenUsed="true" Name="toc 2"/>

UnhideWhenUsed="true" Name="toc 3"/>

UnhideWhenUsed="true" Name="toc 4"/>

UnhideWhenUsed="true" Name="toc 5"/>

UnhideWhenUsed="true" Name="toc 6"/>

UnhideWhenUsed="true" Name="toc 7"/>

UnhideWhenUsed="true" Name="toc 8"/>

UnhideWhenUsed="true" Name="toc 9"/>

Name="Normal Indent"/>

Name="footnote text"/>

Name="annotation text"/>

Name="header"/>

Name="footer"/>

Name="index heading"/>

UnhideWhenUsed="true" QFormat="true" Name="caption"/>

Name="table of figures"/>

Name="envelope address"/>

Name="envelope return"/>

Name="footnote reference"/>

Name="annotation reference"/>

Name="line number"/>

Name="page number"/>

Name="endnote reference"/>

Name="endnote text"/>

Name="table of authorities"/>

Name="macro"/>

Name="toa heading"/>

Name="List"/>

Name="List Bullet"/>

Name="List Number"/>

Name="List 2"/>

Name="List 3"/>

Name="List 4"/>

Name="List 5"/>

Name="List Bullet 2"/>

Name="List Bullet 3"/>

Name="List Bullet 4"/>

Name="List Bullet 5"/>

Name="List Number 2"/>

Name="List Number 3"/>

Name="List Number 4"/>

Name="List Number 5"/>

Name="Closing"/>

Name="Signature"/>

UnhideWhenUsed="true" Name="Default Paragraph Font"/>

Name="Body Text"/>

Name="Body Text Indent"/>

Name="List Continue"/>

Name="List Continue 2"/>

Name="List Continue 3"/>

Name="List Continue 4"/>

Name="List Continue 5"/>

Name="Message Header"/>

Name="Salutation"/>

Name="Date"/>

Name="Body Text First Indent"/>

Name="Body Text First Indent 2"/>

Name="Note Heading"/>

Name="Body Text 2"/>

Name="Body Text 3"/>

Name="Body Text Indent 2"/>

Name="Body Text Indent 3"/>

Name="Block Text"/>

Name="Hyperlink"/>

Name="FollowedHyperlink"/>

Name="Document Map"/>

Name="Plain Text"/>

Name="E-mail Signature"/>

Name="HTML Top of Form"/>

Name="HTML Bottom of Form"/>

Name="Normal (Web)"/>

Name="HTML Acronym"/>

Name="HTML Address"/>

Name="HTML Cite"/>

Name="HTML Code"/>

Name="HTML Definition"/>

Name="HTML Keyboard"/>

Name="HTML Preformatted"/>

Name="HTML Sample"/>

Name="HTML Typewriter"/>

Name="HTML Variable"/>

Name="Normal Table"/>

Name="annotation subject"/>

Name="No List"/>

Name="Outline List 1"/>

Name="Outline List 2"/>

Name="Outline List 3"/>

Name="Table Simple 1"/>

Name="Table Simple 2"/>

Name="Table Simple 3"/>

Name="Table Classic 1"/>

Name="Table Classic 2"/>

Name="Table Classic 3"/>

Name="Table Classic 4"/>

Name="Table Colorful 1"/>

Name="Table Colorful 2"/>

Name="Table Colorful 3"/>

Name="Table Columns 1"/>

Name="Table Columns 2"/>

Name="Table Columns 3"/>

Name="Table Columns 4"/>

Name="Table Columns 5"/>

Name="Table Grid 1"/>

Name="Table Grid 2"/>

Name="Table Grid 3"/>

Name="Table Grid 4"/>

Name="Table Grid 5"/>

Name="Table Grid 6"/>

Name="Table Grid 7"/>

Name="Table Grid 8"/>

Name="Table List 1"/>

Name="Table List 2"/>

Name="Table List 3"/>

Name="Table List 4"/>

Name="Table List 5"/>

Name="Table List 6"/>

Name="Table List 7"/>

Name="Table List 8"/>

Name="Table 3D effects 1"/>

Name="Table 3D effects 2"/>

Name="Table 3D effects 3"/>

Name="Table Contemporary"/>

Name="Table Elegant"/>

Name="Table Professional"/>

Name="Table Subtle 1"/>

Name="Table Subtle 2"/>

Name="Table Web 1"/>

Name="Table Web 2"/>

Name="Table Web 3"/>

Name="Balloon Text"/>

Name="Table Theme"/>

Name="List Paragraph"/>

Name="Intense Quote"/>

Name="Subtle Emphasis"/>

Name="Intense Emphasis"/>

Name="Subtle Reference"/>

Name="Intense Reference"/>

UnhideWhenUsed="true" Name="Bibliography"/>

UnhideWhenUsed="true" QFormat="true" Name="TOC Heading"/>

Name="Grid Table 1 Light Accent 1"/>

Name="Grid Table 6 Colorful Accent 1"/>

Name="Grid Table 7 Colorful Accent 1"/>

Name="Grid Table 1 Light Accent 2"/>

Name="Grid Table 6 Colorful Accent 2"/>

Name="Grid Table 7 Colorful Accent 2"/>

Name="Grid Table 1 Light Accent 3"/>

Name="Grid Table 6 Colorful Accent 3"/>

Name="Grid Table 7 Colorful Accent 3"/>

Name="Grid Table 1 Light Accent 4"/>

Name="Grid Table 6 Colorful Accent 4"/>

Name="Grid Table 7 Colorful Accent 4"/>

Name="Grid Table 1 Light Accent 5"/>

Name="Grid Table 6 Colorful Accent 5"/>

Name="Grid Table 7 Colorful Accent 5"/>

Name="Grid Table 1 Light Accent 6"/>

Name="Grid Table 6 Colorful Accent 6"/>

Name="Grid Table 7 Colorful Accent 6"/>

Name="List Table 1 Light Accent 1"/>

Name="List Table 6 Colorful Accent 1"/>

Name="List Table 7 Colorful Accent 1"/>

Name="List Table 1 Light Accent 2"/>

Name="List Table 6 Colorful Accent 2"/>

Name="List Table 7 Colorful Accent 2"/>

Name="List Table 1 Light Accent 3"/>

Name="List Table 6 Colorful Accent 3"/>

Name="List Table 7 Colorful Accent 3"/>

Name="List Table 1 Light Accent 4"/>

Name="List Table 6 Colorful Accent 4"/>

Name="List Table 7 Colorful Accent 4"/>

Name="List Table 1 Light Accent 5"/>

Name="List Table 6 Colorful Accent 5"/>

Name="List Table 7 Colorful Accent 5"/>

Name="List Table 1 Light Accent 6"/>

Name="List Table 6 Colorful Accent 6"/>

Name="List Table 7 Colorful Accent 6"/>

/* Style Definitions */

table.MsoNormalTable

{mso-style-name:"Table Normal";

mso-tstyle-rowband-size:0;

mso-tstyle-colband-size:0;

mso-style-noshow:yes;

mso-style-priority:99;

mso-style-parent:"";

mso-padding-alt:0cm 5.4pt 0cm 5.4pt;

mso-para-margin:0cm;

mso-para-margin-bottom:.0001pt;

mso-pagination:widow-orphan;

font-size:10.0pt;

font-family:"Calibri","sans-serif";

mso-bidi-font-family:"Times New Roman";}



DOI: https://doi.org/10.19106/JMedSci005104201907

Article Metrics

Abstract views : 1799 | views : 1980


Bookmark and Share


Copyright (c) 2019 Wira Prihatin Siregar, Gontar Alamsyah Siregar, Taufik Sungkar

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.