Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
March-2019 Volume 19 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2019 Volume 19 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma

  • Authors:
    • Huan Zhou
    • Shun Tan
    • Hong Li
    • Xiangtao Lin
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Central South University, Xiangya School of Medicine, Affiliated Haikou Hospital, Haikou, Hainan 570208, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2125-2136
    |
    Published online on: January 22, 2019
       https://doi.org/10.3892/mmr.2019.9886
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

AT‑rich interaction domain 1A (ARID1A) and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α (PIK3CA) serve important roles in the formation and development of numerous malignancies including gastric cancer. Accumulating evidence has demonstrated that Epstein‑Barr virus (EBV) is a pathogenic virus associated with gastric cancer. The present study aimed to investigate the association between EBV infection, and the expression levels of ARID1A and PIK3CA in gastric cancer. EBER in situ hybridization was performed to detect EBV infection. Immunohistochemistry was used to assess the expression levels of ARID1A and PIK3CA in gastric cancer and adjacent normal tissues. A total of 58 gastric cancer and 10 adjacent normal tissues were tested for genetic mutations via single nucleotide polymorphism genotyping assays. Fluorescent polymerase chain reaction was used to detect EBV infection; 9.3% (28/300) of gastric cancer samples were positive for EBV, whereas, all adjacent normal tissues were negative. ARID1A and PIK3CA were negatively correlated in gastric cancer (r=‑0.167). The expression levels of ARID1A and PIK3CA in gastric cancer were significantly associated with the depth of invasion of gastric cancer. A total of 62.1% (36/58) of tumor samples exhibited mutations in ARID1A, whereas, 13.8% (8/58) presented mutations in PIK3CA. Notably, EBV‑associated gastric cancer (EBVaGC) samples with PIK3CA mutations additionally exhibited ARID1A mutations. Although in the present study it was identified that ARID1A and PIK3CA were negatively correlated in EBVaGC, further studies are required to investigate the association among ARID1A, PIK3CA and EBV in gastric cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Wu H, Lin W and Tsai K: Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers. Expert Rev Mol Med. 16:e12014. View Article : Google Scholar : PubMed/NCBI

2 

Fang WL, Huang KH, Lan YT, Lin CH, Chang SC, Chen MH, Chao Y, Lin WC, Lo SS, Li AF, et al: Mutations in PI3K/AKT pathway genes and amplifications of PIK3CA are associated with patterns of recurrence in gastric cancers. Oncotarget. 7:6201–6220. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Camargo MC, Kim K, Matsuo K, Torres J, Liao LM, Morgan DR, Michel A, Waterboer T, Zabaleta J, Dominguez RL, et al: Anti-Helicobacter pylori antibody profiles in epstein-Barr virus (EBV)-positive and EBV-negative gastric cancer. Helicobacter. 21:153–157. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Camargo MC, Bowlby R, Chu A, Pedamallu CS, Thorsson V, Elmore S, Mungall AJ, Bass AJ, Gulley ML and Rabkin CS: Validation and calibration of next-generation sequencing to identify Epstein-Barr virus-positive gastric cancer in The cancer genome atlas. Gastric Cancer. 19:676–681. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Liu Y, Yang W, Pan Y, Ji J, Lu Z and Ke Y: Genome-wide analysis of Epstein-Barr virus (EBV) isolated from EBV-associated gastric carcinoma (EBVaGC). Oncotarget. 7:4903–4914. 2016.PubMed/NCBI

6 

Zhang L, Wang C, Yu S, Jia C, Yan J, Lu Z and Chen J: Loss of ARID1A expression correlates with tumor differentiation and tumor progression stage in pancreatic ductal adenocarcinoma. Technol Cancer ResTreat. 17:1–10. 2018.

7 

Wang S, Nassour I, Xiao S, Zhang S, Luo X, Lee J, Li L, Sun X, Nguyen LH, Chuang JC, et al: SWI/SNF component ARID1A restrains pancreatic neoplasia formation. Pancreas. doi:10.1136/gutjnl-2017-315490.

8 

Shen J, Peng Y, Wei L, Zhang W, Yang L, Lan L, Kapoor P, Ju Z, Mo Q, Shih IM, et al: ARID1A deficiency impairs the DNA damage checkpoint and sensitizes cells to PARP inhibitors. Cancer Discov. 5:752–767. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Mathur R, Alver BH, San Roman AK, Wilson BG, Wang X, Agoston AT, Park PJ, Shivdasani RA and Roberts CW: ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice. Nat Genet. 49:296–302. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Abe H, Kaneda A and Fukayama M: Epstein-Barr virus-associated gastric carcinoma: Use of host cell machineries and somatic gene mutations. Pathobiology. 82:212–223. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Wang L, Shan L, Zhang S, Ying J, Xue L, Yuan Y, Xie Y and Lu N: PIK3CA gene mutations and overexpression: Implications for prognostic biomarker and therapeutic target in chinese esophageal squamous cell carcinoma. PLoS One. 9:e1030212014. View Article : Google Scholar : PubMed/NCBI

12 

Park JH, Ryu MH, Park YS, Park SR, Na YS, Rhoo BY and Kang YK: Successful control of heavily pretreated metastatic gastric cancer with the mTOR inhibitor everolimus (RAD001) in a patient with PIK3CA mutation and pS6 overexpression. BMC Cancer. 15:1192015. View Article : Google Scholar : PubMed/NCBI

13 

Wang Q, Shi YL, Zhou K, Wang LL, Yan ZX, Liu YL, Xu LL, Zhao SW, Chu HL, Shi TT, et al: PIK3CA mutation confer resistance to first-line chemotherapy in colorectal cancer. Cell Death Dis. 9:7392018. View Article : Google Scholar : PubMed/NCBI

14 

Li Hong, Tan Shun, Xing Lu, Li Qian and Zhou Huan: Expression and significance of EBV, ARID1A and PIK3CA gene in gastric cancer. Hainan Med J. 29:1344–1347. 2018.

15 

Liu P, Qin K, Wu K, Shi H and Zhang L: The expression and significance of HAND2 in the myenteric plexus of the colon in patients with Hirschsprung's disease. Guangdong Med J. 34:1513–1515. 2013.(In Chinese).

16 

Wang K, Kan J, Yuen ST, Shi ST, Chu KM, Law S, Chan TL, Kan Z, Chan ASY, Tsui WY, et al: Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nature Genetics. 43:1219–1223. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Kanda T, Furuse Y, Oshitani H and Kiyono T: Highly efficient CRISPR/Cas9-mediated cloning and functional characterization of gastric cancer-Derived epstein-Barr virus strains. J Virol. 90:4383–4393. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Zhang L, Wu H, Sun G, Xu X, Sun X and Cao L: Trichloromethane fraction of Incarvillea compacta induces lytic cytotoxicity and apoptosis in Epstein-Barr virus-positive gastric cancer AGS cells. BMC Complem Altern Med. 16:344–354. 2016. View Article : Google Scholar

19 

Gulley ML: Genomic assays for Epstein–Barr virus-positive gastric adenocarcinoma. Exp Mol Med. 47:e1342015. View Article : Google Scholar : PubMed/NCBI

20 

Wang DD: Decreased expression of the ARID1A gene Is associated with poor prognosis in primary gastric Cancer. PLoS One. 7:e403642012. View Article : Google Scholar : PubMed/NCBI

21 

Luchini C, Veronese N, Solmi M, Cho H, Kim J, Chou A, Gill AJ, Faraj SF, Chaux A, Netto GJ, et al: Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: A systematic review and meta-analysis. Oncotarget. 6:39088–39097. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Harada K, Baba Y, Shigaki H, Ishimoto T, Miyake K, Kosumi K, Tokunaga R, Izumi D, Ohuchi M, Nakamura K, et al: Prognostic and clinical impact of PIK3CA mutation in gastric cancer: Pyrosequencing technology and literature review. BMC Cancer. 16:400–407. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Ibarrola-Villava M, Llorca-Cardenosa MJ, Tarazona N, Mongort C, Fleitas T, Perez-Fidalgo JA, Rosello S, Navarro S, Ribas G and Cervantes A: Deregulation of ARID1A, CDH1, cMET and PIK3CA and target-related microRNA expression in gastric cancer. Oncotarget. 6:26935–26945. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Jang SH, Kim KJ, Oh MH, Lee JH and Lee HJ: Clinicopathological significance of elevated PIK3CA expression in gastric cancer. J Gastric Cancer. 16:85–92. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Wu Y, Gu Y, Guo S, Dai Q and Zhang W: Expressing status and correlation of ARID1A and histone H2B on breast cancer. Biomed Res Int 2016. 7593872016.

26 

Wei X, Wang DS, Xi SY, Wu WJ, Chen DL, Zeng ZL, Wang RY, Huang YX, Jin Y, Wang F, et al: Clinicopathologic and prognostic relevance of ARID1A protein loss in colorectal cancer. World J Gastroenterol. 20:18404–18412. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Lee D, Yu EJ, Ham IH, Hur H and Kim YS: AKT inhibition is an effective treatment strategy in ARID1A-deficient gastric cancer cells. Onco Targrts Ther. 10:4153–4159. 2017. View Article : Google Scholar

28 

Zhang Q, Yan HB, Wang J, Cui SJ, Wang XQ, Jiang YH, Feng L, Yang PY and Liu F: Chromatin remodeling gene AT-rich interactive domaincontaining protein 1A suppresses gastric cancer cell proliferation by targeting PIK3CA and PDK1. Oncotarget. 7:46127–46141. 2016.PubMed/NCBI

29 

Giulino-Roth L, Wang K, Macdonald TY, Mathew S, Tam Y, Cronin MT, Palmer G, Lucena-Silva N, Pedrosa F, Pedrosa M, et al: Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes. Blood. 120:5181–5184. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Wu R, Wang T and Shih IeM: The emerging roles of ARID1A in tumor suppression. Cancer Biol Ther. 15:655–664. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Böger C, Krüger S, Behrens HM, Bock S, Haag J, Kalthoff H and Röcken C: Epstein-Barr virus-associated gastric cancer reveals intratumoral heterogeneity of PIK3CA mutations. Ann Oncol. 28:1005–1014. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Kaneda A, Matsusaka K, Aburatani H and Fukayama M: Epstein-Barr virus infection as an epigenetic driver of tumorigenesis. Cancer Res. 72:3445–3450. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Suzuki Y, Enokido Y, Yamada K, Inaba M, Kuwata K, Hanada N, Morishita T, Mizuno S and Wakamatsu N: The effect of rapamycin, NVP-BEZ235, aspirin, and metforminon PI3K/AKT/mTOR signaling pathway of PIK3CA-related overgrowth spectrum (PROS). Oncotarget. 8:45470–45483. 2017. View Article : Google Scholar : PubMed/NCBI

34 

Wang XY, Huang YX, Guo RH, Liu YB, Qian YY, Liu D, Dai XJ, Wei Z, Jin F and Liu YQ: Clinicopathological significance of ROCK1 and PIK3CA expression in nasopharyngeal carcinoma. Exp Ther Med. 13:1064–1068. 2017. View Article : Google Scholar : PubMed/NCBI

35 

Zhang Q, Yan HB, Wang J, Cui SJ, Wang XQ, Jiang YH, Feng L, Yang P Y and Liu F: Chromatin remodeling gene AT-rich interactive domain-containing protein 1A suppresses gastric cancer cell proliferation by targeting PIK3CA and PDK1. Oncotarget. 7:46127–46141. 2016.PubMed/NCBI

36 

Sivachandran N, Dawson CW, Young LS, Liu FF, Middeldorp J and Frappier L: Contributions of the epstein-Barr virus EBNA1 protein to gastric carcinoma. J Virol. 86:60–68. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhou H, Tan S, Li H and Lin X: Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma. Mol Med Rep 19: 2125-2136, 2019.
APA
Zhou, H., Tan, S., Li, H., & Lin, X. (2019). Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma. Molecular Medicine Reports, 19, 2125-2136. https://doi.org/10.3892/mmr.2019.9886
MLA
Zhou, H., Tan, S., Li, H., Lin, X."Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma". Molecular Medicine Reports 19.3 (2019): 2125-2136.
Chicago
Zhou, H., Tan, S., Li, H., Lin, X."Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma". Molecular Medicine Reports 19, no. 3 (2019): 2125-2136. https://doi.org/10.3892/mmr.2019.9886
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou H, Tan S, Li H and Lin X: Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma. Mol Med Rep 19: 2125-2136, 2019.
APA
Zhou, H., Tan, S., Li, H., & Lin, X. (2019). Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma. Molecular Medicine Reports, 19, 2125-2136. https://doi.org/10.3892/mmr.2019.9886
MLA
Zhou, H., Tan, S., Li, H., Lin, X."Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma". Molecular Medicine Reports 19.3 (2019): 2125-2136.
Chicago
Zhou, H., Tan, S., Li, H., Lin, X."Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma". Molecular Medicine Reports 19, no. 3 (2019): 2125-2136. https://doi.org/10.3892/mmr.2019.9886
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team