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Analysis of Key Genes and Pathways Associated with Colorectal Cancer with Microarray Technology

  • Liu, Yan-Jun (Department of General Surgery, The Third People's Hospital of Chengdu, The Second Clinical College Affiliated to Chongqing Medical University) ;
  • Zhang, Shu (Department of General Surgery, The Third People's Hospital of Chengdu, The Second Clinical College Affiliated to Chongqing Medical University) ;
  • Hou, Kang (Department of General Surgery, The Third People's Hospital of Chengdu, The Second Clinical College Affiliated to Chongqing Medical University) ;
  • Li, Yun-Tao (Department of General Surgery, The Third People's Hospital of Chengdu, The Second Clinical College Affiliated to Chongqing Medical University) ;
  • Liu, Zhan (Department of General Surgery, The Third People's Hospital of Chengdu, The Second Clinical College Affiliated to Chongqing Medical University) ;
  • Ren, Hai-Liang (Department of General Surgery, The Third People's Hospital of Chengdu, The Second Clinical College Affiliated to Chongqing Medical University) ;
  • Luo, Dan (Department of General Surgery, The Third People's Hospital of Chengdu, The Second Clinical College Affiliated to Chongqing Medical University) ;
  • Li, Shi-Hong (Department of General Surgery, The Third People's Hospital of Chengdu, The Second Clinical College Affiliated to Chongqing Medical University)
  • Published : 2013.03.30

Abstract

Objective: Microarray data were analyzed to explore key genes and their functions in progression of colorectal cancer (CRC). Methods: Two microarray data sets were downloaded from Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified using corresponding packages of R. Functional enrichment analysis was performed with DAVID tools to uncover their biological functions. Results: 631 and 590 DEGs were obtained from the two data sets, respectively. A total of 32 common DEGs were then screened out with the rank product method. The significantly enriched GO terms included inflammatory response, response to wounding and response to drugs. Two interleukin-related domains were revealed in the domain analysis. KEGG pathway enrichment analysis showed that the PPAR signaling pathway and the renin-angiotensin system were enriched in the DEGs. Conclusions: Our study to systemically characterize gene expression changes in CRC with microarray technology revealed changes in a range of key genes, pathways and function modules. Their utility in diagnosis and treatment now require exploration.

Keywords

References

  1. Ager EI, Neo J, Christophi C (2008). The renin-angiotensin system and malignancy. Carcinogenesis, 29, 1675-84. https://doi.org/10.1093/carcin/bgn171
  2. Aizat AA, Shahpudin SN, Mustapha MA, et al (2011). Association of Arg72Pro of P53 polymorphism with colorectal cancer susceptibility risk in Malaysian population. Asian Pac J Cancer Prev, 12, 2909-13.
  3. Amid A, Wan Chik WD, Jamal P, Hashim YZ (2012). Microarray and quantitative PCR analysis of gene expression profiles in response to treatment with tomato leaf extract in mcf-7 breast cancer cells. Asian Pac J Cancer Prev, 13, 6319-25. https://doi.org/10.7314/APJCP.2012.13.12.6319
  4. Ansel KM, Harris RB, Cyster JG (2002). CXCL13 is required for B1 cell homing, natural antibody production, and body cavity immunity. Immunity, 16, 67-76. https://doi.org/10.1016/S1074-7613(01)00257-6
  5. Bernardi CC, Ribeiro Ede S, Cavalli IJ, et al (2010). Amplification and deletion of the ACHE and BCHE cholinesterase genes in sporadic breast cancer. Cancer Genet Cytogenet, 197, 158-65. https://doi.org/10.1016/j.cancergencyto.2009.10.011
  6. Bigler J, Whitton J, Lampe JW, et al (2001). CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk. Cancer Res, 61, 3566-9.
  7. Brass N, Racz A, Heckel D, et al (1997). Amplification of the genes BCHE and SLC2A2 in 40% of squamous cell carcinoma of the lung. Cancer Res, 57, 2290-4.
  8. Burrell LM, Johnston CI, Tikellis C, Cooper ME (2004). ACE2, a new regulator of the renin-angiotensin system. Trends Endocrinol Metab, 15, 166-9. https://doi.org/10.1016/j.tem.2004.03.001
  9. Davies H, Hunter C, Smith R, et al (2005). Somatic mutations of the protein kinase gene family in human lung cancer. Cancer Res, 65, 7591-5.
  10. de Wit M, Fijneman RJ, Verheul HM, et al (2012). Proteomics in colorectal cancer translational research: Biomarker discovery for clinical applications. Clin Biochem, 46, 466-79.
  11. Dong P, He XW, Gu J, et al (2011). Vimentin significantly promoted gallbladder carcinoma metastasis. Chin Med J Beijing, 124, 4236.
  12. Doniger SW, Salomonis N, Dahlquist KD, et al (2003). MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data. Genome Biol, 4, R7. https://doi.org/10.1186/gb-2003-4-1-r7
  13. Draghici S, Khatri P, Tarca AL, et al (2007). A systems biology approach for pathway level analysis. Genome Res, 17, 1537-45. https://doi.org/10.1101/gr.6202607
  14. Edgar R, Domrachev M, Lash AE (2002). Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res, 30, 207-10. https://doi.org/10.1093/nar/30.1.207
  15. El-Haibi CP, Singh R, Sharma PK, et al (2011). CXCL13 mediates prostate cancer cell proliferation through JNK signalling and invasion through ERK activation. Cell Prolif, 44, 311-9. https://doi.org/10.1111/j.1365-2184.2011.00757.x
  16. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  17. Garber K (2010). Of Ephs and ephrins: companies target guidance molecules in cancer. J Natl Cancer Inst, 102, 1692-4. https://doi.org/10.1093/jnci/djq479
  18. George AJ, Thomas WG, Hannan RD (2010). The reninangiotensin system and cancer: old dog, new tricks. Nat Rev Cancer, 10, 745-59. https://doi.org/10.1038/nrc2945
  19. Greystoke A, Dean E, Saunders MP, et al (2012). Multi-level evidence that circulating CK18 is a biomarker of tumour burden in colorectal cancer. Br J Cancer, 107, 1518-24. https://doi.org/10.1038/bjc.2012.416
  20. Hong F, Breitling R, McEntee CW, et al (2006). RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics, 22, 2825-7. https://doi.org/10.1093/bioinformatics/btl476
  21. Hong Y, Ho KS, Eu KW, Cheah PY (2007). A susceptibility gene set for early onset colorectal cancer that integrates diverse signaling pathways: implication for tumorigenesis. Clin Cancer Res, 13, 1107-14. https://doi.org/10.1158/1078-0432.CCR-06-1633
  22. Huang da W, Sherman BT, Lempicki RA (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc, 4, 44-57.
  23. Hubner RA, Muir KR, Liu JF, et al (2006). Genetic variants of UGT1A6 influence risk of colorectal adenoma recurrence. Clin Cancer Res, 12, 6585-9. https://doi.org/10.1158/1078-0432.CCR-06-0903
  24. Hunter S, Apweiler R, Attwood TK, et al (2009). InterPro: the integrative protein signature database. Nucleic Acids Res, 37, D211-5. https://doi.org/10.1093/nar/gkn785
  25. Johnson V, Lipton LR, Cummings C, et al (2005). Analysis of somatic molecular changes, clinicopathological features, family history, and germline mutations in colorectal cancer families: evidence for efficient diagnosis of HNPCC and for the existence of distinct groups of non-HNPCC families. J Med Genet, 42, 756-62. https://doi.org/10.1136/jmg.2005.031245
  26. Koizumi K, Kozawa Y, Ohashi Y, et al (2007). CCL21 promotes the migration and adhesion of highly lymph node metastatic human non-small cell lung cancer Lu-99 in vitro. Oncol Rep, 17, 1511-6.
  27. Lisabeth EM, Fernandez C, Pasquale EB (2012). Cancer somatic mutations disrupt functions of the EphA3 receptor tyrosine kinase through multiple mechanisms. Biochemistry, 51, 1464-75. https://doi.org/10.1021/bi2014079
  28. Liu N, Fang XD, Vadis Q (2012). CD73 as a novel prognostic biomarker for human colorectal cancer. J Surg Oncol, 106, 918-9; author reply 920. https://doi.org/10.1002/jso.23159
  29. Lokshin AE, Winans M, Landsittel D, et al (2006). Circulating IL-8 and anti-IL-8 autoantibody in patients with ovarian cancer. Gynecol Oncol, 102, 244-51. https://doi.org/10.1016/j.ygyno.2005.12.011
  30. Marx J (2004). Cancer research. Inflammation and cancer: the link grows stronger. Science, 306, 966-8. https://doi.org/10.1126/science.306.5698.966
  31. Meng W, Zhu HH, Xu ZF, et al (2012). Serum M2-pyruvate kinase: A promising non-invasive biomarker for colorectal cancer mass screening. World J Gastrointest Oncol, 4, 145-51. https://doi.org/10.4251/wjgo.v4.i6.145
  32. Menin C, Scaini MC, De Salvo GL, et al (2006). Association between MDM2-SNP309 and age at colorectal cancer diagnosis according to p53 mutation status. J Natl Cancer Inst, 98, 285-8. https://doi.org/10.1093/jnci/djj054
  33. Montenegro MF, Ruiz-Espejo F, Campoy FJ, et al (2006). Acetyland butyrylcholinesterase activities decrease in human colon adenocarcinoma. J Mol Neurosci, 30, 51-4. https://doi.org/10.1385/JMN:30:1:51
  34. Pan D, Sun N, Cheung KH, et al (2003). PathMAPA: a tool for displaying gene expression and performing statistical tests on metabolic pathways at multiple levels for Arabidopsis. BMC bioinformatics, 4, 56. https://doi.org/10.1186/1471-2105-4-56
  35. Panse J, Friedrichs K, Marx A, et al (2008). Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients. Br J Cancer, 99, 930-8. https://doi.org/10.1038/sj.bjc.6604621
  36. Pasquale EB (2010). Eph receptors and ephrins in cancer:bidirectional signalling and beyond. Nat Rev Cancer, 10, 165-80. https://doi.org/10.1038/nrc2806
  37. Ricci-Vitiani L, Fabrizi E, Palio E, De Maria R (2009). Colon cancer stem cells. J Mol Med (Berl), 87, 1097-104. https://doi.org/10.1007/s00109-009-0518-4
  38. Rubie C, Frick VO, Pfeil S, et al (2007). Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer. World J Gastroenterol, 13, 4996-5002.
  39. Sabates-Bellver J, Van der Flier LG, de Palo M, et al (2007). Transcriptome profile of human colorectal adenomas. Mol Cancer Res, 5, 1263-75. https://doi.org/10.1158/1541-7786.MCR-07-0267
  40. Samowitz WS, Wolff RK, Curtin K, et al (2006). Interactions between CYP2C9 and UGT1A6 polymorphisms and nonsteroidal anti-inflammatory drugs in colorectal cancer prevention. Clin Gastroenterol Hepatol, 4, 894-901. https://doi.org/10.1016/j.cgh.2006.04.021
  41. Shields JD, Kourtis IC, Tomei AA, et al (2010). Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science, 328, 749-52. https://doi.org/10.1126/science.1185837
  42. Singh S, Singh R, Sharma PK, et al (2009). Serum CXCL13 positively correlates with prostatic disease, prostate-specific antigen and mediates prostate cancer cell invasion, integrin clustering and cell adhesion. Cancer Lett, 283, 29-35. https://doi.org/10.1016/j.canlet.2009.03.022
  43. Smyth GK (2004). Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol, 3, Article3.
  44. Surawska H, Ma PC, Salgia R (2004). The role of ephrins and Eph receptors in cancer. Cytokine Growth Factor Rev, 15, 419-33. https://doi.org/10.1016/j.cytogfr.2004.09.002
  45. Takahashi M, Cuatrecasas M, Balaguer F, et al (2012). The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer. PLoS One, 7, e46684. https://doi.org/10.1371/journal.pone.0046684
  46. Takahashi N, Goto T, Kusudo T, et al (2005). [The structures and functions of peroxisome proliferator-activated receptors (PPARs)]. Nihon Rinsho, 63, 557-64.
  47. Talseth-Palmer BA, McPhillips M, Groombridge C, et al (2010). MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer. Hered Cancer Clin Pract, 8, 5. https://doi.org/10.1186/1897-4287-8-5
  48. Todaro M, Francipane MG, Medema JP, Stassi G (2010). Colon cancer stem cells: promise of targeted therapy. Gastroenterology, 138, 2151-62. https://doi.org/10.1053/j.gastro.2009.12.063
  49. Wood LD, Calhoun ES, Silliman N, et al (2006). Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum Mutat, 27, 1060-1.
  50. Xi HQ, Zhao P (2011). Clinicopathological significance and prognostic value of EphA3 and CD133 expression in colorectal carcinoma. J Clin Pathol, 64, 498-503. https://doi.org/10.1136/jcp.2010.087213
  51. Yang WL, Frucht H (2001). Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells. Carcinogenesis, 22, 1379-83. https://doi.org/10.1093/carcin/22.9.1379
  52. Zhai XH, Yu JK, Yang FQ, Zheng S (2012). Identification of a new protein biomarker for colorectal cancer diagnosis. Mol Med Report, 6, 444-8.

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