Advertisement

Ecotoxicology

, Volume 20, Issue 5, pp 1026–1032 | Cite as

Integration of gene chip and topological network techniques to screen a candidate biomarker gene (CBG) for predication of the source water carcinogenesis risks on mouse Mus musculus

  • Jie Sun
  • Shupei Cheng
  • Aimin Li
  • Rui Zhang
  • Bing Wu
  • Yan Zhang
  • Xuxiang Zhang
Article

Abstract

Screening of a candidate biomarker gene (CBG) to predicate the carcinogenesis risks in the Yangtze River source of drinking water in Nanjing area (YZR-SDW-NJ) on mouse (Mus musculus) was conducted in this research. The effects of YZR-SDW-NJ on the genomic transcriptional expression levels were measured by the GeneChip® Mouse Genome and data treated by the GO database analysis. The 298 genes discovered as the differently expressed genes (DEGs) were down-regulated and their values were ≤−1.5-fold. Of the 298 DEGs, 25 were cancer-related genes selected as the seed genes to build a topological network map with Genes2Networks software, only 7 of them occurred at the constructed map. Smad2 gene was at the constructed map center and could be identified as a candidate biomarker gene (CBG) primarily which involves the genesis and development of colorectal, leukemia, lung and prostate cancers directly. Analysis of the gene signal pathway further approved that smad2 gene had the relationships closely to other 16 cancer-related genes and could be used as a CBG to indicate the carcinogenic risks in YZR-SDW-NJ. The data suggest that integration of gene chip and network techniques may be a way effectively to screen a CBG. And the parameter values for further judgment of the CBG through signal pathway relationship analysis also will be discussed.

Keywords

Source water Mouse Gene chip Topological network Candidate biomarker gene Carcinogenesis 

Notes

Acknowledgments

This research was supported by the Key Program of National Nature Science Foundation, China [50938004], Social Development Plan of Science and Technology for Jiangsu Province, China [BE2009668], and Nanjing University 985 program [2011HJXY0318].

References

  1. Ahlborn GJ, Nelson GM, Ward WO, Knapp G, Allen JW, Ouyang M, Roop BC, Chen Y, O'Brien T, Kitchin KT, Delker DA (2008) Dose response evaluation of gene expression profiles in the skin of k6/odc mice exposed to sodium arsenite. Toxicol Appl Pharmacol 227(3):400–416. doi: 10.1016/j.taap.2007.10.029 CrossRefGoogle Scholar
  2. Alm E, Arkin AP (2003) Biological networks. Curr Opin Struct Biol 13(2):193–202. doi: 10.1016/s0959-440x(03)00031-9 CrossRefGoogle Scholar
  3. Andrew AS, Bernardo V, Warnke LA, Davey JC, Hampton T, Mason RA, Thorpe JE, Ihnat MA, Hamilton JW (2007) Exposure to arsenic at levels found in us drinking water modifies expression in the mouse lung. Toxicol Sci 100(1):75–87. doi: 10.1093/toxsci/kfm200 CrossRefGoogle Scholar
  4. Ang CW, Nedjadi T, Sheikh AA, Tweedle EM, Tonack S, Honap S, Jenkins RE, Park BK, Schwarte-Waldhoff I, Khattak I, Azadeh B, Dodson A, Kalirai H, Neoptolemos JP, Rooney PS, Costello E (2010) Smad4 loss is associated with fewer s100a8-positive monocytes in colorectal tumors and attenuated response to s100a8 in colorectal and pancreatic cancer cells. Carcinogenesis 31(9):1541–1551. doi: 10.1093/carcin/bgq137 CrossRefGoogle Scholar
  5. Bandyopadhyay S, Chiang CY, Srivastava J, Gersten M, White S, Bell R, Kurschner C, Martin CH, Smoot M, Sahasrabudhe S, Barber DL, Chanda SK, Ideker T (2010) A human map kinase interactome. Nat Methods 7(10):U801–U850. doi: 10.1038/nmeth.1506 CrossRefGoogle Scholar
  6. Berger SI, Posner JM, Ma’ayan A (2007) Genes2networks: connecting lists of gene symbols using mammalian protein interactions databases. BMC Bioinform 8. doi: 10.1186/1471-2105-8-372
  7. Bespalova IN, Durner M, Ritter BP, Angelo GW, Rossy-Fullana E, Carrion-Baralt J, Schmeidler J, Silverman JM (2010) Non-synonymous variants in the amacr gene are associated with schizophrenia. Schizophr Res 124(1–3):208–215. doi: 10.1016/j.schres.2010.08.040 CrossRefGoogle Scholar
  8. Boffetta P (2010) Biomarkers in cancer epidemiology: an integrative approach. Carcinogenesis 31(1):121–126. doi: 10.1093/carcin/bgp269 CrossRefGoogle Scholar
  9. Brown KA, Ham AJL, Clark CN, Meller N, Law BK, Chytil A, Cheng N, Pietenpol JA, Moses HL (2008) Identification of novel smad2 and smad3 associated proteins in response to tgf-beta 1. J Cell Biochem 105(2):596–611. doi: 10.1002/jcb.21860 CrossRefGoogle Scholar
  10. Cebrat M, Strzadala L, Kisielow P (2004) Wnt inhibitory factor-1: a candidate for a new player in tumorigenesis of intestinal epithelial cells. Cancer Lett 206(1):107–113. doi: 10.1016/j.canlet.2003.10.024 CrossRefGoogle Scholar
  11. Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen GH, Mukherjee C, Shi YF, Gelinas C, Fan YJ, Nelson DA, Jin SK, White E (2006) Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Canc Cell 10(1):51–64. doi: 10.1016/j.ccr.2006.06.001 CrossRefGoogle Scholar
  12. Emilsson V, Thorleifsson G, Zhang B, Leonardson AS, Zink F, Zhu J, Carlson S, Helgason A, Walters GB, Gunnarsdottir S, Mouy M, Steinthorsdottir V, Eiriksdottir GH, Bjornsdottir G, Reynisdottir I, Gudbjartsson D, Helgadottir A, Jonasdottir A, Jonasdottir A, Styrkarsdottir U, Gretarsdottir S, Magnusson KP, Stefansson H, Fossdal R, Kristjansson K, Gislason HG, Stefansson T, Leifsson BG, Thorsteinsdottir U, Lamb JR, Gulcher JR, Reitman ML, Kong A, Schadt EE, Stefansson K (2008) Genetics of gene expression and its effect on disease. Nature 452(7186):U422–U423. doi: 10.1038/Nature06758 CrossRefGoogle Scholar
  13. Feng XH, Derynck R (2005) Specificity and versatility in tgf-beta signaling through smads. Annu Rev Cell Dev Biol 21:659–693. doi: 10.1146/annurev.cellbio.21.022404.142018 CrossRefGoogle Scholar
  14. Fontana L, Delort L, Joumard L, Rabiau N, Bosviel R, Satih S, Guy L, Boiteux JP, Bignon YJ, Chamoux A, Bernard-Gallon DJ (2009) Genetic polymorphisms in cyp1a1, cyp1b1, comt, gstp1 and nat2 genes and association with bladder cancer risk in a French cohort. Anticancer Res 29(5):1631–1635Google Scholar
  15. Gao J, Zhao WX, Xue FS, Zhou LJ, Xu SQ, Ding N (2010) Early administration of propofol protects against endotoxin-induced acute lung injury in rats by inhibiting the tgf-beta 1-smad2 dependent pathway. Inflamm Res 59(7):491–500. doi: 10.1007/s00011-009-0110-y CrossRefGoogle Scholar
  16. Jacobson EM, Hugo ER, Tuttle TR, Papoian R, Ben-Jonathan N (2010) Unexploited therapies in breast and prostate cancer: blockade of the prolactin receptor. Trends Endocrinol Metab 21(11):691–698. doi: 10.1016/j.tem.2010.08.004 CrossRefGoogle Scholar
  17. Jiang ZQ, Gui SB, Zhang YZ (2010) Differential gene expression by fiber-optic bead array and pathway in adrenocorticotrophin-secreting pituitary adenomas. Chin Med J Peking 123(23):3455–3461. doi: 10.3760/cma.j.issn.0366-6999.2010.23.015 Google Scholar
  18. Johanson V, Ahlman H, Bernhardt P, Jansson S, Kolby L, Persson F, Stenman G, Sward C, Wangberg B, Stridsberg M, Nilsson O (2007) A transplantable human medullary thyroid carcinoma as a model for ret tyrosine kinase-driven tumorigenesis. Endocr Relat Cancer 14(2):433–444. doi: 10.1677/Erc-06-0033 CrossRefGoogle Scholar
  19. Lemarchand K, Masson L, Brousseau R (2004) Molecular biology and DNA microarray technology for microbial quality monitoring of water. Crit Rev Microbiol 30(3):145–172. doi: 10.1080/10408410490435142 CrossRefGoogle Scholar
  20. Li Y, Agarwal P, Rajagopalan D (2008) A global pathway crosstalk network. Bioinformatics 24(12):1442–1447. doi: 10.1093/bioinformatics/btn200 CrossRefGoogle Scholar
  21. Lin S, Yang J, Yu L, Sun L (2010) Mutation and phosphorylation of p53 may switch tgf-beta from a tumor suppressor to a tumor promoter. Proc Am Assoc Cancer Res Annu Meet 51:964–965Google Scholar
  22. MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17(1):9–26. doi: 10.1016/j.devcel.2009.06.016 CrossRefGoogle Scholar
  23. Makarov DV, Loeb S, Getzenberg RH, Partin AW (2009) Biomarkers for prostate cancer. Annu Rev Med 60:139–151. doi: 10.1146/annurev.med.60.042307.110714 CrossRefGoogle Scholar
  24. Massague J (2008) Tgf beta in cancer. Cell 134(2):215–230. doi: 10.1016/j.cell.2008.07.001 CrossRefGoogle Scholar
  25. Perez DS, Handa RJ, Yang RSH, Campain JA (2008) Gene expression changes associated with altered growth and differentiation in benzo a pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol 28(4):491–508. doi: 10.1002/jat.1301 CrossRefGoogle Scholar
  26. Perttu MC, Martikainen PM, Huhtala HSA, Blauer M, Tammela TLJ, Tuohimaa PJ, Syvala H (2006) Altered levels of smad2 and smad4 are associated with human prostate carcinogenesis. Prostate Cancer Prostatic Dis 9(2):185–189. doi: 10.1038/sj.pcan.4500871 CrossRefGoogle Scholar
  27. Richardson SD, Plewa MJ, Wagner ED, Schoeny R, DeMarini DM (2007) Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research. Mutat Res-Rev Mutat Res 636(1–3):178–242. doi: 10.1016/j.mrrev.2007.09.001 Google Scholar
  28. Robinson JF, Yu XZ, Hong SW, Griffith WC, Beyer R, Kim E, Faustman EM (2009) Cadmium-induced differential toxicogenomic response in resistant and sensitive mouse strains undergoing neurulation. Toxicol Sci 107(1):206–219. doi: 10.1093/toxsci/kfn221 CrossRefGoogle Scholar
  29. Sahmel J, Devlin K, Paustenbach D, Hollins D, Gaffney S (2010) The role of exposure reconstruction in occupational human health risk assessment: current methods and a recommended framework. Crit Rev Toxicol 40(9):799–843. doi: 10.3109/10408444.2010.501052 CrossRefGoogle Scholar
  30. Sears C, Armstrong SA (2007) Microarrays to identify new therapeutic strategies for cancer. In: Advances in cancer research, vol 96. Elsevier Academic Press Inc., San Diego, pp 51-74. doi: 10.1016/s0065-230x(06)96003-5
  31. Shen L, Wu JY, Lin GF, Shen JH, Westendorf J, Huehnerfuss H (2003) The mutagenic potentials of tap water samples in shanghai. Chemosphere 52(9):1641–1646. doi: 10.1016/s0045-6535(03)00504-6 CrossRefGoogle Scholar
  32. Taylor IW, Wrana JL (2008) Snapshot: the tgf beta pathway interactome. Cell 133(2). doi: 10.1016/j.cell.2008.04.007
  33. Tomioka N, Morita K, Kobayashi N, Tada M, Itoh T, Saitoh S, Kondo M, Takahashi N, Kataoka A, Nakanishi K, Takahashi M, Kamiyama T, Ozaki M, Hirano T, Todo S (2010) Array comparative genomic hybridization analysis revealed four genomic prognostic biomarkers for primary gastric cancers. Cancer Genet Cytogenet 201(1):6–14. doi: 10.1016/j.cancergencyto.2010.04.017 CrossRefGoogle Scholar
  34. Trakooljul N, Hicks JA, Liu HC (2010) Identification of target genes and pathways associated with chicken microrna mir-143. Anim Genet 41(4):357–364. doi: 10.1111/j.1365-2052.2009.02015.x Google Scholar
  35. Won KY, Kim YW, Park YK (2010) Expression of smad and its signalling cascade in osteosarcoma. Pathology 42(3):242–247. doi: 10.3109/00313021003631288 CrossRefGoogle Scholar
  36. Wu YL, Chen HG, Li ZL, Sun LW, Qu MM, Li M, Kong ZM (2008) Genotoxicity evaluation of drinking water sources in human peripheral blood lymphocytes using the comet assay. J Environ Sci 20(4):487–491CrossRefGoogle Scholar
  37. Wu B, Zhang X, Zhang X, Yasun A, Zhang Y, Zhao D, Ford T, Cheng S (2009) Semi-volatile organic compounds and trace elements in the Yangtze river source of drinking water. Ecotoxicology 18(6):707–714. doi: 10.1007/s10646-009-0331-4 CrossRefGoogle Scholar
  38. Wu B, Zhang Y, Zhang XX, Cheng SP (2010) Health risk from exposure of organic pollutants through drinking water consumption in Nanjing, China. Bull Environ Contam Toxicol 84(1):46–50. doi: 10.1007/s00128-009-9900-8 CrossRefGoogle Scholar
  39. Yang JY, Wahdan-Alaswad R, Danielpour D (2009) Critical role of smad2 in tumor suppression and transforming growth factor-beta-induced apoptosis of prostate epithelial cells. Cancer Res 69(6):2185–2190. doi: 10.1158/0008-5472.can-08-3961 CrossRefGoogle Scholar
  40. Zingg JM, Libinaki R, Lai CQ, Meydani M, Gianello R, Ogru E, Azzi A (2010) Modulation of gene expression by alpha-tocopherol and alpha-tocopheryl phosphate in thp-1 monocytes. Free Radic Biol Med 49(12):1989–2000. doi: 10.1016/j.freeradbiomed.2010.09.034 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jie Sun
    • 1
  • Shupei Cheng
    • 1
  • Aimin Li
    • 1
  • Rui Zhang
    • 1
  • Bing Wu
    • 1
  • Yan Zhang
    • 1
  • Xuxiang Zhang
    • 1
  1. 1.State Key Laboratory of Pollution Control & Resource Reuse and School of the EnvironmentNanjing UniversityNanjingChina

Personalised recommendations