Genomic expression profiling and bioinformatics analysis of pancreatic cancer

Han,Dong‑Yan; Fu,Da; Xi,Hao; Li,Qian‑Yu; Feng,Li‑Jin; Zhang,Wei; Ji,Guo; Xiao,Jia‑Cheng; Wei,Qing

doi:10.3892/mmr.2015.3917

Genomic expression profiling and bioinformatics analysis of pancreatic cancer

Authors:
- Dong‑Yan Han
- Da Fu
- Hao Xi
- Qian‑Yu Li
- Li‑Jin Feng
- Wei Zhang
- Guo Ji
- Jia‑Cheng Xiao
- Qing Wei
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Affiliations: Department of Pathology, Shanghai Tenth People's Hospital, Shanghai 200072, P.R. China
Published online on: June 11, 2015 https://doi.org/10.3892/mmr.2015.3917
Pages: 4133-4140
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Pancreatic cancer is a polygenic disease and the fourth leading cause of cancer-associated mortality worldwide; however, the tumorigenesis of pancreatic cancer remains poorly understood. Research at a molecular level, which includes the exploration of biomarkers for early diagnosis and specific targets for therapy, may effectively aid in the diagnosis of pancreatic cancer in its early stages and in the development of targeted molecular‑biological approaches for treatment, thus improving prognosis. By conducting expression profiling in para‑carcinoma, carcinoma and relapse of human pancreatic tissues, 319 genes or transcripts with differential expression levels >3‑fold between these tissue types were identified. Further analysis with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that the translation, nucleus assembly processes and molecular functions associated with vitamin B6 and pyridoxal phosphate binding in pancreatic carcinoma were abnormal. Pancreatic cancer was additionally identified to be closely associated with certain autoimmune diseases, including type I diabetes mellitus and systemic lupus erythematosus.

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1	Ghaneh P, Smith R, Tudor-Smith C, Raraty M and Neoptolemos JP: Neoadjuvant and adjuvant strategies for pancreatic cancer. Eur J Surg Oncol. 34:297–305. 2008. View Article : Google Scholar
2	Sugimura T, Terada M, Yokota J, Hirohashi S and Wakabayashi K: Multiple genetic alterations in human carcinogenesis. Environ Health Perspect. 98:5–12. 1992. View Article : Google Scholar : PubMed/NCBI
3	Neoptolemos JP, Urrutia R, Abbruzzese JL and Büchler MW: Pancreatic Cancer. Chapter. 21:498–505. 2010.
4	Rafael S, Veganzones S, Vidaurreta M, de la Orden V and Maestro ML: Effect of β-catenin alterations in the prognosis of patients with sporadic colorectal cancer. J Cancer Res Ther. 10:591–596. 2014.PubMed/NCBI
5	López-Casas PP and López-Fernández LA: Gene-expression profiling in pancreatic cancer. Expert Rev Mol Diagn. 10:591–601. 2010. View Article : Google Scholar : PubMed/NCBI
6	Maitra A, Kern SE and Hruban RH: Molecular pathogenesis of pancreatic cancer. Best Pract Res Clin Gastroenterol. 20:211–226. 2006. View Article : Google Scholar : PubMed/NCBI
7	Li Q and Xu W: Novel anticancer targets and drug discovery in post genomic age. Curr Med Chem Anticancer Agents. 5:53–63. 2005. View Article : Google Scholar : PubMed/NCBI
8	Downward J: Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 3:11–22. 2003. View Article : Google Scholar : PubMed/NCBI
9	Morris JP IV, Wang SC and Hebrok M: KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer. 10:683–695. 2010. View Article : Google Scholar : PubMed/NCBI
10	Wang Z, Banerjee S, Ahmad A, Li Y, Azmi AS, Gunn JR, Kong D, Bao B, Ali S, Gao J, et al: Activated K-ras and INK4a/Arf deficiency cooperate during the development of pancreatic cancer by activation of Notch and NF-κB signaling pathways. PLoS One. 6:e205372011. View Article : Google Scholar
11	Lauth M and Toftgård R: Hedgehog signaling and pancreatic tumor development. Adv Cancer Res. 110:1–17. 2011. View Article : Google Scholar : PubMed/NCBI
12	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 :
13	Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, Miller DK, Wilson PJ, Patch AM, Wu J, et al: Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 491:399–405. 2012. View Article : Google Scholar : PubMed/NCBI
14	Hidalgo M: Pancreatic cancer. N Engl J Med. 362:1605–1617. 2010. View Article : Google Scholar : PubMed/NCBI
15	Shain AH, Salari K, Giacomini CP and Pollack JR: Integrative genomic and functional profiling of the pancreatic cancer genome. BMC Genomics. 14:6242013. View Article : Google Scholar : PubMed/NCBI
16	Mohr S, Leikauf GD, Keith G and Rihn BH: Microarrays as cancer keys: An array of possibilities. J Clin Oncol. 20:3165–3175. 2002. View Article : Google Scholar : PubMed/NCBI
17	Chang ZY, Sun R, Ma YS, Fu D, Lai XL, Li YS, Wang XH, Zhang XP, Lv ZW, Cong XL, et al: Differential gene expression of the key signalling pathway in para-carcinoma, carcinoma and relapse human pancreatic cancer. Cell Biochem Funct. 32:258–267. 2014. View Article : Google Scholar
18	Nakamura T, Furukawa Y, Nakagawa H, Tsunoda T, Ohigashi H, Murata K, Ishikawa O, Ohgaki K, Kashimura N, Miyamoto M, et al: Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection. Oncogene. 23:2385–2400. 2004. View Article : Google Scholar : PubMed/NCBI
19	Backman V, Wallace MB, Perelman LT, Arendt JT, Gurjar R, Müller MG, Zhang Q, Zonios G, Kline E, McGilligan JA, et al: Detection of preinvasive cancer cells. Nature. 406:35–36. 2000. View Article : Google Scholar : PubMed/NCBI
20	Schernhammer E, Wolpin B, Rifai N, Cochrane B, Manson JA, Ma J, Giovannucci E, Thomson C, Stampfer MJ and Fuchs C: Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts. Cancer Res. 67:5553–5560. 2007. View Article : Google Scholar : PubMed/NCBI
21	Johansson M, Relton C, Ueland PM, Vollset SE, Midttun Ø, Nygård O, Slimani N, Boffetta P, Jenab M, Clavel-Chapelon F, et al: Serum B vitamin levels and risk of lung cancer. JAMA. 303:2377–2385. 2010. View Article : Google Scholar : PubMed/NCBI
22	Wu W, Kang S and Zhang D: Association of vitamin B6, vitamin B12 and methionine with risk of breast cancer: A dose-response meta-analysis. Br J Cancer. 109:1926–1944. 2013. View Article : Google Scholar : PubMed/NCBI
23	Dubois EL: The effect of the L. E. cell test on the clinical picture of systemic lupus erythematosus. Ann Intern Med. 38:1265–1294. 1953. View Article : Google Scholar : PubMed/NCBI
24	Smedby KE, Hjalgrim H, Askling J, Chang ET, Gregersen H, Porwit-MacDonald A, Sundström C, Akerman M, Melbye M, Glimelius B, et al: Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. J Natl Cancer Inst. 98:51–60. 2006. View Article : Google Scholar : PubMed/NCBI
25	Björnådal L, Löfström B, Yin L, Lundberg IE and Ekbom A: Increased cancer incidence in a Swedish cohort of patients with systemic lupus erythematosus. Scand J Rheumatol. 31:66–71. 2002. View Article : Google Scholar : PubMed/NCBI
26	Cibere J, Sibley J and Haga M: Systemic lupus erythematosus and the risk of malignancy. Lupus. 10:394–400. 2001. View Article : Google Scholar : PubMed/NCBI
27	Pettersson T, Pukkala E, Teppo L and Friman C: Increased risk of cancer in patients with systemic lupus erythematosus. Ann Rheum Dis. 51:437–439. 1992. View Article : Google Scholar : PubMed/NCBI
28	Bernatsky S, Ramsey-Goldman R, Rajan R, Boivin JF, Joseph L, Lachance S, Cournoyer D, Zoma A, Manzi S, Ginzler E, et al: Non-Hodgkin's lymphoma in systemic lupus erythematosus. Ann Rheum Dis. 64:1507–1509. 2005. View Article : Google Scholar : PubMed/NCBI
29	Ramsey-Goldman R, Mattai SA, Schilling E, Chiu YL, Alo CJ, Howe HL and Manzi S: Increased risk of malignancy in patients with systemic lupus erythematosus. J Investig Med. 46:217–222. 1998.PubMed/NCBI
30	Bernatsky S, Ramsey-Goldman R, Isenberg D, Isenberg D, Rahman A, Dooley MA, Sibley J, Boivin JF, Joseph L, Armitage J, et al: Hodgkin's lymphoma in systemic lupus erythematosus. Rheumatology (Oxford). 46:830–832. 2007. View Article : Google Scholar
31	Landgren O, Engels EA, Pfeiffer RM, Gridley G, Mellemkjaer L, Olsen JH, Kerstann KF, Wheeler W, Hemminki K, Linet MS, et al: Autoimmunity and susceptibility to Hodgkin lymphoma: A population-based case-control study in Scandinavia. J Natl Cancer Inst. 98:1321–1330. 2006. View Article : Google Scholar : PubMed/NCBI
32	Gayed M, Bernatsky S, Ramsey-Goldman R, Clarke A and Gordon C: Lupus and cancer. Lupus. 18:479–485. 2009. View Article : Google Scholar : PubMed/NCBI
33	Bernatsky S, Boivin JF, Joseph L, Manzi S, Ginzler E, Gladman DD, Urowitz M, Fortin PR, Petri M, Barr S, et al: Mortality in systemic lupus erythematosus. Arthritis Rheum. 54:2550–2557. 2006. View Article : Google Scholar : PubMed/NCBI
34	Thomas E, Brewster DH, Black RJ and Macfarlane GJ: Risk of malignancy among patients with rheumatic conditions. Int J Cancer. 88:497–502. 2000. View Article : Google Scholar : PubMed/NCBI
35	Mellemkjér L, Andersen V, Linet MS, et al: Non-Hodgkin's lymphoma and other cancers among a cohort of patients with systemic lupus erythematosus. Arthritis Rheum. 40:761–768. 1997. View Article : Google Scholar
36	Bernatsky S, Ramsey-Goldman R and Clarke AE: Revisiting the issue of malignancy risk in systemic lupus erythematosus. Curr Rheumatol Rep. 7:476–481. 2005. View Article : Google Scholar : PubMed/NCBI
37	Ruiz-Irastorza G, Ugarte A, Egurbide MV, Garmendia M, Pijoan JI, Martinez-Berriotxoa A and Aguirre C: Antimalarials may influence the risk of malignancy in systemic lupus erythematosus. Ann Rheum Dis. 66:815–817. 2007. View Article : Google Scholar : PubMed/NCBI
38	Bernatsky S, Boivin JF, Joseph L, Rajan R, Zoma A, Manzi S, Ginzler E, Urowitz M, Gladman D, Fortin PR, et al: An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum. 52:1481–1490. 2005. View Article : Google Scholar : PubMed/NCBI
39	Akerblom HK and Knip M: Putative environmental factors in Type 1 diabetes. Diabetes Metab Rev. 14:31–67. 1998. View Article : Google Scholar : PubMed/NCBI
40	Stevens RJ, Roddam AW and Beral V: Pancreatic cancer in type 1 and young-onset diabetes: Systematic review and meta-analysis. Br J Cancer. 96:507–509. 2007. View Article : Google Scholar : PubMed/NCBI
41	Zendehdel K, Nyrén O, Ostenson CG, Adami HO, Ekbom A and Ye W: Cancer incidence in patients with type 1 diabetes mellitus: A population-based cohort study in Sweden. J Natl Cancer Inst. 95:1797–1800. 2003. View Article : Google Scholar : PubMed/NCBI