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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
June-2018 Volume 15 Issue 6

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
June-2018 Volume 15 Issue 6

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

Functional analysis of gene expression profiling‑based prediction in bladder cancer

  • Authors:
    • Ji‑Ping Wang
    • Ji‑Yan Leng
    • Rong‑Kui Zhang
    • Li Zhang
    • Bei Zhang
    • Wen‑Yan Jiang
    • Lan Tong
  • View Affiliations / Copyright

    Affiliations: Department of Radiology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Geratology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 8417-8423
    |
    Published online on: March 28, 2018
       https://doi.org/10.3892/ol.2018.8370
  • 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

The present study aimed to analyze the modification of gene expression in bladder cancer (BC) by identifying significant differentially expressed genes (DEGs) and functionally assess them using bioinformatics analysis. To achieve this, two microarray datasets, GSE24152 (which included 10 fresh tumor tissue samples from urothelial bladder carcinoma patients and 7 benign mucosa samples from the bladder), and GSE42089 (which included 10 tissues samples from urothelial cell carcinoma patients and 8 tissues samples from the normal bladder), were downloaded from the Gene Expression Omnibus database for further analysis. Differentially expressed genes (DEGs) were screened between benign the mucosa and control groups in GSE24152 and GSE42089 datasets. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed on overlapping DEGs identified in GSE24152 and GSE42089. Protein‑protein interaction (PPI) networks and sub‑networks were then constructed to identify key genes and main pathways. GO terms analysis was also performed for the selected clusters. In total, 1,325 DEGs in GSE24152 and 647 DEGs in GSE42089 were screened, in which 619 common DEGs were identified. The DEGs were mainly enriched in pathways and GO terms associated with mitotic and chromosome assembly, including nucleosome assembly, spindle checkpoint and DNA replication. In the interaction network, progesterone receptor (PGR), MAF bZIP transcription factor G (MAFG), cell division cycle 6 (CDC6) and members of the minichromosome maintenance family (MCMs) were identified as key genes. Histones were also considered to be significant factors in BC. Nucleosome assembly and sequence‑specific DNA binding were the most significant clustered GO terms. In conclusion, the DEGs, including PGR, MAFG, CDC6 and MCMs, and those encoding the core histone family were closely associated with the development of BC via pathways associated with mitotic and chromosome assembly.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Ploeg M, Aben KK and Kiemeney LA: The present and future burden of urinary bladder cancer in the world. World J Urol. 27:289–293. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Karavitakis M, Msaouel P, Michalopoulos V and Koutsilieris M: Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples. Anticancer Res. 34:2937–2942. 2014.PubMed/NCBI

4 

Eisenberg MS, Boorjian SA, Cheville JC, Thompson RH, Thapa P, Kaushik D and Frank I: The SPARC score: A multifactorial outcome prediction model for patients undergoing radical cystectomy for bladder cancer. J Urol. 190:2005–2010. 2013. View Article : Google Scholar : PubMed/NCBI

5 

James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, Crundwell M, Sizer B, Sreenivasan T, Hendron C, et al: Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 366:1477–1488. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Shen Y, Wang X, Jin Y, Lu J, Qiu G and Wen X: Differentially expressed genes and interacting pathways in bladder cancer revealed by bioinformatic analysis. Mol Med Rep. 10:1746–1752. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Zhou N, Singh K, Mir MC, Parker Y, Lindner D, Dreicer R, Ecsedy JA, Zhang Z, Teh BT, Almasan A and Hansel DE: The investigational aurora kinase a inhibitor MLN8237 induces defects in cell viability and cell-cycle progression in malignant bladder cancer cells in vitro and in vivo. Clin Cancer Res. 19:1717–1728. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Zhang Z, Furge KA, Yang XJ, Teh BT and Hansel DE: Comparative gene expression profiling analysis of urothelial carcinoma of the renal pelvis and bladder. BMC Med Genomics. 3:582010. View Article : Google Scholar : PubMed/NCBI

9 

Gautier L, Cope L, Bolstad BM and Irizarry RA: Affy-analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 20:307–315. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Smyth GK: Limma: Linear models for microarray dataBioinformatics and computational biology solutions using R and Bioconductor. Springer; New York, NY: pp. 397–420. 2005, View Article : Google Scholar

11 

Chen H and Boutros PC: VennDiagram: A package for the generation of highly-customizable Venn and Euler diagrams in R. BMC Bioinformatics. 12:352011. View Article : Google Scholar : PubMed/NCBI

12 

Wickham H: ggplot2: Elegant graphics for data analysis. Springer; New York, NY: 2009, View Article : Google Scholar

13 

Hulsegge I, Kommadath A and Smits MA: Globaltest and GOEAST: Two different approaches for Gene Ontology analysis. BMC Proc. 3 Suppl 4:S102009. View Article : Google Scholar : PubMed/NCBI

14 

Galperin MY and Fernández-Suárez XM: The 2012 nucleic acids research database issue and the online molecular biology database collection. Nucleic Acids Res. 40:(Database Issue). D1–D8. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Huang da W, Sherman BT and Lempicki RA: Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1–13. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Smoot ME, Ono K, Ruscheinski J, Wang PL and Ideker T: Cytoscape 2.8: New features for data integration and network visualization. Bioinformatics. 27:431–432. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Martin A, Ochagavia ME, Rabasa LC, Miranda J, Fernandez-de-Cossio J and Bringas R: BisoGenet: A new tool for gene network building, visualization and analysis. BMC Bioinformatics. 11:912010. View Article : Google Scholar : PubMed/NCBI

18 

Bader GD, Betel D and Hogue CW: BIND: The biomolecular interaction network database. Nucleic Acids Res. 31:248–250. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Nepusz T, Yu H and Paccanaro A: Detecting overlapping protein complexes in protein-protein interaction networks. Nat Methods. 9:471–472. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Mulac-Jericevic B and Conneely OM: Reproductive tissue selective actions of progesterone receptors. Reproduction. 128:139–146. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Miyamoto H, Yang Z, Chen YT, Ishiguro H, Uemura H, Kubota Y, Nagashima Y, Chang YJ, Hu YC, Tsai MY, et al: Promotion of bladder cancer development and progression by androgen receptor signals. J Natl Cancer Inst. 99:558–568. 2007. View Article : Google Scholar : PubMed/NCBI

23 

De León-Nava MA, Nava K, Soldevila G, López-Griego L, Chávez-Ríos JR, Vargas-Villavicencio JA and Morales-Montor J: Immune sexual dimorphism: Effect of gonadal steroids on the expression of cytokines, sex steroid receptors, and lymphocyte proliferation. J Steroid Biochem Mol Biol. 113:57–64. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Loyola A and Almouzni G: Histone chaperones, a supporting role in the limelight. Biochim Biophys Acta. 1677:3–11. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Vaquero A, Loyola A and Reinberg D: The constantly changing face of chromatin. Sci Aging Knowledge Environ. 2003:RE42003. View Article : Google Scholar : PubMed/NCBI

26 

Esteller M: Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 8:286–298. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Schneider AC, Heukamp LC, Rogenhofer S, Fechner G, Bastian PJ, von Ruecker A, Müller SC and Ellinger J: Global histone H4K20 trimethylation predicts cancer-specific survival in patients with muscle-invasive bladder cancer. BJU Int. 108:E290–E296. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Kim K, Punj V, Choi J, Heo K, Kim JM, Laird PW and An W: Gene dysregulation by histone variant H2A.Z in bladder cancer. Epigenetics Chromatin. 6:342013. View Article : Google Scholar : PubMed/NCBI

29 

Motohashi H, O'Connor T, Katsuoka F, Engel JD and Yamamoto M: Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors. Gene. 294:1–12. 2002. View Article : Google Scholar : PubMed/NCBI

30 

Kyo M, Yamamoto T, Motohashi H, Kamiya T, Kuroita T, Tanaka T, Engel JD, Kawakami B and Yamamoto M: Evaluation of MafG interaction with Maf recognition element arrays by surface plasmon resonance imaging technique. Genes Cells. 9:153–164. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Shimokawa N, Kumaki I, Qiu CH, Ohmiya Y, Takayama K and Koibuchi N: Extracellular acidification enhances DNA binding activity of MafG-FosB heterodimer. J Cell Physiol. 205:77–85. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Shaulian E and Karin M: AP-1 as a regulator of cell life and death. Nat Cell Biol. 4:E131–E136. 2002. View Article : Google Scholar : PubMed/NCBI

33 

Avouac J, Palumbo K, Tomcik M, Zerr P, Dees C, Horn A, Maurer B, Akhmetshina A, Beyer C, Sadowski A, et al: Inhibition of activator protein 1 signaling abrogates transforming growth factor β-mediated activation of fibroblasts and prevents experimental fibrosis. Arthritis Rheum. 64:1642–1652. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Gopalakrishnan A and Kong Tony AN: Anticarcinogenesis by dietary phytochemicals: Cytoprotection by Nrf2 in normal cells and cytotoxicity by modulation of transcription factors NF-kappa B and AP-1 in abnormal cancer cells. Food Chem Toxicol. 46:1257–1270. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Borlado LR and Méndez J: CDC6: From DNA replication to cell cycle checkpoints and oncogenesis. Carcinogenesis. 29:237–243. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Brun C, Guénoche A and Jacq B: Approach of the functional evolution of duplicated genes in Saccharomyces cerevisiae using a new classification method based on protein-protein interaction data. J Struct Funct Genomics. 3:213–224. 2003. View Article : Google Scholar : PubMed/NCBI

37 

Korkolopoulou P, Givalos N, Saetta A, Goudopoulou A, Gakiopoulou H, Thymara I, Thomas-Tsagli E and Patsouris E: Minichromosome maintenance proteins 2 and 5 expression in muscle-invasive urothelial cancer: A multivariate survival study including proliferation markers and cell cycle regulators. Human Pathol. 36:899–907. 2005. View Article : Google Scholar

38 

Murphy N, Ring M, Heffron CC, King B, Killalea AG, Hughes C, Martin CM, McGuinness E, Sheils O and O'Leary JJ: p16INK4A, CDC6, and MCM5: Predictive biomarkers in cervical preinvasive neoplasia and cervical cancer. J Clin Pathol. 58:525–534. 2005. View Article : Google Scholar : PubMed/NCBI

39 

Borlado LR and Méndez J: CDC6: From DNA replication to cell cycle checkpoints and oncogenesis. Carcinogenesis. 29:237–243. 2008. View Article : Google Scholar : PubMed/NCBI

40 

Yao Z and Mishra L: Cancer stem cells and hepatocellular carcinoma. Cancer Biol Ther. 8:1691–1698. 2009. View Article : Google Scholar : PubMed/NCBI

41 

Luo JH: Oncogenic activity of MCM7 transforming cluster. World J Clin Oncol. 2:120–124. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang JP, Leng JY, Zhang RK, Zhang L, Zhang B, Jiang WY and Tong L: Functional analysis of gene expression profiling‑based prediction in bladder cancer. Oncol Lett 15: 8417-8423, 2018.
APA
Wang, J., Leng, J., Zhang, R., Zhang, L., Zhang, B., Jiang, W., & Tong, L. (2018). Functional analysis of gene expression profiling‑based prediction in bladder cancer. Oncology Letters, 15, 8417-8423. https://doi.org/10.3892/ol.2018.8370
MLA
Wang, J., Leng, J., Zhang, R., Zhang, L., Zhang, B., Jiang, W., Tong, L."Functional analysis of gene expression profiling‑based prediction in bladder cancer". Oncology Letters 15.6 (2018): 8417-8423.
Chicago
Wang, J., Leng, J., Zhang, R., Zhang, L., Zhang, B., Jiang, W., Tong, L."Functional analysis of gene expression profiling‑based prediction in bladder cancer". Oncology Letters 15, no. 6 (2018): 8417-8423. https://doi.org/10.3892/ol.2018.8370
Copy and paste a formatted citation
x
Spandidos Publications style
Wang JP, Leng JY, Zhang RK, Zhang L, Zhang B, Jiang WY and Tong L: Functional analysis of gene expression profiling‑based prediction in bladder cancer. Oncol Lett 15: 8417-8423, 2018.
APA
Wang, J., Leng, J., Zhang, R., Zhang, L., Zhang, B., Jiang, W., & Tong, L. (2018). Functional analysis of gene expression profiling‑based prediction in bladder cancer. Oncology Letters, 15, 8417-8423. https://doi.org/10.3892/ol.2018.8370
MLA
Wang, J., Leng, J., Zhang, R., Zhang, L., Zhang, B., Jiang, W., Tong, L."Functional analysis of gene expression profiling‑based prediction in bladder cancer". Oncology Letters 15.6 (2018): 8417-8423.
Chicago
Wang, J., Leng, J., Zhang, R., Zhang, L., Zhang, B., Jiang, W., Tong, L."Functional analysis of gene expression profiling‑based prediction in bladder cancer". Oncology Letters 15, no. 6 (2018): 8417-8423. https://doi.org/10.3892/ol.2018.8370
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