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Screening of Differentially Expressed Genes Related to Bladder Cancer and Functional Analysis with DNA Microarray

  • Huang, Yi-Dong (Department of Pediatric Surgery, West China Hospital of Sichuan University) ;
  • Shan, Wei (Department of Pediatric Surgery, West China Hospital of Sichuan University) ;
  • Zeng, Li (Department of Pediatric Surgery, West China Hospital of Sichuan University) ;
  • Wu, Yang (Department of Pediatric Surgery, West China Hospital of Sichuan University)
  • Published : 2013.08.30

Abstract

Objective: The purpose of this study was to identify genes related to bladder cancer with samples from normal and disease cases by microarray chip. Methods: After downloading the gene expression profile GSE3167 from Gene Expression Omnibus database which includes 50 bladder samples, comprising 9 normal and 41 disease samples, differentially expressed genes were identified with packages in R language. The selected differentially expressed genes were further analyzed using bioinformatics methods. Firstly, molecular functions, biological processes and cell component analysis were researched by software Gestalt. Then, software String was used to search interaction relationships among differentially expressed genes, and hub genes of the network were selected. Finally, by using plugins of software Cytoscape, Mcode and Bingo, module analysis of hub-genes was performed. Results: A total of 221 genes were identified as differentially expressed by comparing normal and disease bladder samples, and a network as well as the hub gene C1QBP was obtained from the network. The C1QBP module had the closest relationship to production of molecular mediators involved in inflammatory responses. Conclusion: We obtained differentially expressed genes of bladder cancer by microarray, and both PRDX2 and YWHAZ in the module with hub gene C1QBP were most significantly related to production of molecular mediators involved in inflammatory responses. From knowledge of inflammatory responses and cancer, our results showed that, the hub gene and its module could induce inflammation in bladder cancer. These related genes are candidate bio-markers for bladder cancer diagnosis and might be helpful in designing novel therapies.

Keywords

References

  1. Amamoto R, Yagi M, Song Y, et al (2011). Mitochondrial p32/C1QBP is highly expressed in prostate cancer and is associated with shorter prostate-specific antigen relapse time after radical prostatectomy. Cancer Sci, 102, 639-47. https://doi.org/10.1111/j.1349-7006.2010.01828.x
  2. Avritscher EBC, Cooksley CD, Grossman HB, et al (2006). Clinical model of lifetime cost of treating bladder cancer and associated complications. Urol, 68, 549-53. https://doi.org/10.1016/j.urology.2006.03.062
  3. Baris D, Karagas MR, Verrill C, et al (2009). A case-control study of smoking and bladder cancer risk: emergent patterns over time. J Natl Cancer Inst, 101, 1553-61. https://doi.org/10.1093/jnci/djp361
  4. Benjamini Y, Hochberg Y (1995). Controlling the False Discovery Rate - A Practical and Powerful Approach to Multiple Testing. J R Stat Soc Series B Stat Methodol, 57, 289-300.
  5. Brokstad KA, Kalland K-H, Russell WC , Matthews DA (2001). Mitochondrial protein p32 can accumulate in the nucleus. Biochem Biophys Res Commun, 281, 1161-9. https://doi.org/10.1006/bbrc.2001.4473
  6. Ching CB, Hansel DE (2010). Expanding therapeutic targets in bladder cancer: the PI3K/Akt/mTOR pathway. Lab Invest, 90, 1406-14. https://doi.org/10.1038/labinvest.2010.133
  7. Deb TB , Datta K (1996). Molecular cloning of human fibroblast hyaluronic acid-binding protein confirms its identity with P-32, a protein co-purified with splicing factor SF2 - Kyaluronic acid-binding protein as P-32 protein, co-purified with splicing factor SF2. J Biol Chem, 271, 2206-12. https://doi.org/10.1074/jbc.271.4.2206
  8. Dedio J, Mueller-Esterl W (1996). Kininogen binding protein p33/gC1qR is localized in the vesicular fraction of endothelial cells. FEBS Lett, 399, 255-8. https://doi.org/10.1016/S0014-5793(96)01339-7
  9. Duncan D, Prodduturi N, Zhang B (2010). WebGestalt2: an updated and expanded version of the Web-based Gene Set Analysis Toolkit. BMC Bioinformatics, 11.
  10. Dunham I, Kundaje A, Aldred SF, et al (2012). An integrated encyclopedia of DNA elements in the human genome. Nature, 489, 57-74. https://doi.org/10.1038/nature11247
  11. Dyrskjot L, Kruhoffer M, Thykjaer T, et al (2004). Gene expression in the urinary bladder: A common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res, 64, 4040-8. https://doi.org/10.1158/0008-5472.CAN-03-3620
  12. Fujita A, Sato JR, Rodrigues LdO, et al (2006). Evaluating different methods of microarray data normalization. BMC Bioinformatics, 7, 469. https://doi.org/10.1186/1471-2105-7-469
  13. Gakis G, Schwentner C, Todenhoefer T , Stenzl A (2012). Current status of molecular markers for prognostication and outcome in invasive bladder cancer. BJU Int, 110, 233-7. https://doi.org/10.1111/j.1464-410X.2011.10839.x
  14. Ghebrehiwet B, Lim B-L, Peerschke EIB, et al (1994). Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular “heads” of C1q. J Exp Med, 179, 1809-21. https://doi.org/10.1084/jem.179.6.1809
  15. Goldberg AD, Allis CD, Bernstein E (2007). Epigenetics: A landscape takes shape. Cell, 128, 635-8. https://doi.org/10.1016/j.cell.2007.02.006
  16. Gupta S, Datta K (1991). Possible role of hyaluronectin on cell-adhesion in rat histiocytoma. Exp Cell Res, 195, 386-94. https://doi.org/10.1016/0014-4827(91)90388-B
  17. Heney NM (1992). Natural-history of superficial bladder-cancer-prognostic features and long-team disease couse. Urol Clin North Am, 19, 429-33.
  18. Jeong H, Tombor B, Albert R, et al (2000). The large-scale organization of metabolic networks. Nature, 407, 651-4. https://doi.org/10.1038/35036627
  19. Jiang J, Zhang Y, Krainer AR , Xu RM (1999). Crystal structure of human p32, a doughnut-shaped acidic mitochondrial matrix protein. Proc Natl Acad Sci U S A, 96, 3572-7. https://doi.org/10.1073/pnas.96.7.3572
  20. Kamal A , Datta K (2006). Upregulation of hyaluronan binding protein 1 (HABP1/p32/gC1qR) is associated with cisplatin induced apoptosis. Apoptosis, 11, 861-74. https://doi.org/10.1007/s10495-006-5396-4
  21. Li Z, Zhao J, Du Y, et al (2008). Down-regulation of 14-3-3zeta suppresses anchorage-independent growth of lung cancer cells through anoikis activation. Proc Natl Acad Sci U S A, 105, 162-7. https://doi.org/10.1073/pnas.0710905105
  22. Majumdar M, Meenakshi J, Goswami SK, Datta K (2002). Hyaluronan binding protein 1 (HABP1)/C1QBP/p32 is an endogenous substrate for MAP kinase and is translocated to the nucleus upon mitogenic stimulation. Biochem Biophys Res Commun, 291, 829-37. https://doi.org/10.1006/bbrc.2002.6491
  23. Malmstrom PU, Larsson A, Johansson S (1993). Urinary fibronectin in diagnosis and follow-up of patients with urinary bladder cancer. Br J Urol, 72, 307-10. https://doi.org/10.1111/j.1464-410X.1993.tb00723.x
  24. Matthews DA, Russell WC (1998). Adenovirus core protein V interacts with p32-a protein which is associated with both the mitochondria and the nucleus. J Gen Virol, 79, 1677-85.
  25. Mitra AP, Datar RH, Cote RJ (2006). Molecular pathways in invasive bladder cancer: New insights into mechanisms, progression, and target identification. J Clin Oncol, 24, 5552-64. https://doi.org/10.1200/JCO.2006.08.2073
  26. Neal CL, Yu D (2010). 14-3-3zeta as a prognostic marker and therapeutic target for cancer. Expert Opin Ther Targets, 14, 1343-54. https://doi.org/10.1517/14728222.2010.531011
  27. Niemantsverdriet M, Wagner K, Visser M, Backendorf C (2008). Cellular functions of 14-3-3 zeta in apoptosis and cell adhesion emphasize its oncogenic character. Oncogene, 27, 1315-9. https://doi.org/10.1038/sj.onc.1210742
  28. Noh DY, Ahn SJ, Lee RA, et al (2001). Overexpression of peroxiredoxin in human breast cancer. Anticancer Res, 21, 2085-90.
  29. Parkin DM (2008). The global burden of urinary bladder cancer. Scand J Urol Nephrol, 42, 12-20.
  30. Pasin E, Josephson DY, Mitra AP, et al (2008). Superficial bladder cancer: an update on etiology, molecular development, classification, and natural history. Rev Urol, 10, 31-43.
  31. Proctor I, Stoeber K, Williams GH (2010). Biomarkers in bladder cancer. Histopathology (Oxford), 57, 1-13.
  32. Puzio-Kuter AM, Castillo-Martin M, Kinkade CW, et al (2009). Inactivation of p53 and Pten promotes invasive bladder cancer. Genes Dev, 23, 675-80. https://doi.org/10.1101/gad.1772909
  33. Ranganathan S, Ganguly AK, Datta K (1994). Evidence for presence of hyaluronan binding protein on spermatozoa and its possible involvement in sperm function. Mol Reprod Dev, 38, 69-76. https://doi.org/10.1002/mrd.1080380112
  34. Rao CM, Deb TB, Datta K (1996). Hyaluronic acid induced hyaluronic acid binding protein phosphorylation and inositol triphosphate formation in lymphocytes. Biochem Mol Biol Int, 40, 327-37.
  35. Reef S, Shifman O, Oren M, Kimchi A (2007). The autophagic inducer smARF interacts with and is stabilized bythe mitochondrial p32 protein. Oncogene, 26, 6677-83. https://doi.org/10.1038/sj.onc.1210485
  36. Rubinstein DB, Stortchevoi A, Boosalis M, et al (2004). Receptor for the globular heads of Clq (gClq-R, p33, hyaluronan-binding protein) is preferentially expressed by adenocarcinoma cells. Int J Cancer, 110, 741-50. https://doi.org/10.1002/ijc.20105
  37. Ryu J, Park SG, Park BC, et al (2011). Proteomic analysis of psoriatic skin tissue for identification of differentially expressed proteins: up-regulation of GSTP1, SFN and PRDX2 in psoriatic skin. Int J Mol Med, 28, 785-92.
  38. Sengupta A, Banerjee B, Tyagi RK, Datta K (2005). Golgi localization and dynamics of hyaluronan binding protein 1 (HABP1/p32/C1QBP) during the cell cycle. Cell Res, 15, 183-6. https://doi.org/10.1038/sj.cr.7290284
  39. Siegel RL, Jemal A, Thun MJ, et al (2008). Trends in the incidence of colorectal cancer in relation to county-level poverty among blacks and whites. J Natl Med, 100, 1441-4.
  40. Smith-Pearson PS, Kooshki M, Spitz DR, et al (2008). Decreasing peroxiredoxin II expression decreases glutathione, alters cell cycle distribution, and sensitizes glioma cells to ionizing radiation and H(2)O(2). Free Radic Biol Med, 45, 1178-89. https://doi.org/10.1016/j.freeradbiomed.2008.07.015
  41. Soini Y, Kallio JP, Hirvikoski P, et al (2006). Oxidative/nitrosative stress and peroxiredoxin 2 are associated with grade and prognosis of human renal carcinoma. APMIS, 114, 329-37. https://doi.org/10.1111/j.1600-0463.2006.apm_315.x
  42. Szklarczyk D, Franceschini A, Kuhn M, et al (2011). The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res, 39, D561-8. https://doi.org/10.1093/nar/gkq973
  43. Tong AHY, Drees B, Nardelli G, et al (2002). A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules. Science, 295, 321-4. https://doi.org/10.1126/science.1064987
  44. Troyanskaya O, Cantor M, Sherlock G, et al (2001). Missing value estimation methods for DNA microarrays. Bioinformatics, 17, 520-5. https://doi.org/10.1093/bioinformatics/17.6.520
  45. Wen Z, Wang Z, Wang S, et al (2011). Discovery of molecular mechanisms of traditional Chinese medicinal formula Si-Wu-Tang using gene expression microarray and connectivity map. PLoS One, 6, e18278. https://doi.org/10.1371/journal.pone.0018278
  46. Yu HY, Greenbaum D, Lu HX, et al (2004). Genomic analysis of essentiality within protein networks. Trends Genet, 20, 227-31. https://doi.org/10.1016/j.tig.2004.04.008
  47. Zaharieva BM, Simon R, Diener PA, et al (2003). High-throughput tissue microarray analysis of 11q13 gene amplification (CCNDI, FGF3, FGF4, EMSI) in urinary bladder cancer. J Pathol, 201, 603-8. https://doi.org/10.1002/path.1481
  48. Zang L, Palmer Toy D, Hancock WS, et al (2004). Proteomic analysis of ductal carcinoma of the breast using laser capture microdissection, LC-MS, and 16O/18O isotopic labeling. J Proteome Res, 3, 604-12. https://doi.org/10.1021/pr034131l
  49. Zhu Z, Shen Z, Xu C (2012). Inflammatory pathways as promising targets to increase chemotherapy response in bladder cancer. Mediators Inflamm, 2012, 528690.

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