Skip to main content
Top
Published in: Tumor Biology 3/2015

01-03-2015 | Research Article

RETRACTED ARTICLE: A comprehensive analysis of candidate genes and pathways in pancreatic cancer

Authors: Jie Liu, Jun Li, Hali Li, Aidong Li, Biou Liu, Liou Han

Published in: Tumor Biology | Issue 3/2015

Login to get access

Abstract

The study aimed to dissect the molecular mechanism of pancreatic cancer by a range of bioinformatics approaches. Three microarray datasets (GSE32676, GSE21654, and GSE14245) were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) with logarithm of fold change (|logFC|) >0.585 and p value <0.05 were identified between pancreatic cancer samples and normal controls. Transcription factors (TFs) were selected from the DEGs based on TRASFAC database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the DEGs using The Database for Annotation, Visualization and Integrated Discovery (p value <0.05), followed by construction of protein-protein interaction (PPI) network using Search Tool for the Retrieval of Interacting Genes software. Latent pathway identification analysis was applied to analyze the DEGs-related pathways crosstalk and the pathways with high weight value were included in the pathway crosstalk network using Cytoscape. Sixty-five DEGs were screened out. CCAAT/enhancer-binding protein delta (CEBPD), FBJ osteosarcoma oncogene B (FOSB), Stratifin (SFN), Krüppel-like factor 5 (KLF5), Pentraxin 3 (PTX3), and nuclear receptor subfamily 4, group A, member 3 (NR4A3) were important TFs. Interleukin-6 (IL-6) was the hub node of the PPI network. DEGs were significantly enriched in NOD-like receptor signaling pathway which was primarily interacted with inflammation and immune related pathways (cytosolic DNA-sensing, hematopoietic cell lineage, intestinal immune network for IgA production and chemokine pathways). The study suggested CEBPD, FOSB, SFN, KLF5, PTX3, NR4A3, IL-6, and NOD-like receptor pathways were involved in pancreatic cancer.
Literature
1.
go back to reference Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137–50.CrossRefPubMed Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137–50.CrossRefPubMed
2.
go back to reference Seufferlein T, Bachet J, Van Cutsem E, Rougier P. Pancreatic adenocarcinoma: ESMO–ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 suppl 7:vii33–40.CrossRefPubMed Seufferlein T, Bachet J, Van Cutsem E, Rougier P. Pancreatic adenocarcinoma: ESMO–ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 suppl 7:vii33–40.CrossRefPubMed
3.
go back to reference Loos M, Kleeff J, Friess H, Büchler MW. Surgical treatment of pancreatic cancer. Ann N Y Acad Sci. 2008;1138(1):169–80.CrossRefPubMed Loos M, Kleeff J, Friess H, Büchler MW. Surgical treatment of pancreatic cancer. Ann N Y Acad Sci. 2008;1138(1):169–80.CrossRefPubMed
4.
go back to reference Biankin AV, Waddell N, Kassahn KS, Gingras M-C, Muthuswamy LB, Johns AL, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 2012;491(7424):399–405.CrossRefPubMedPubMedCentral Biankin AV, Waddell N, Kassahn KS, Gingras M-C, Muthuswamy LB, Johns AL, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 2012;491(7424):399–405.CrossRefPubMedPubMedCentral
5.
go back to reference Maupin KA, Sinha A, Eugster E, Miller J, Ross J, Paulino V, et al. Glycogene expression alterations associated with pancreatic cancer epithelial-mesenchymal transition in complementary model systems. PLoS One. 2010;5(9):e13002.CrossRefPubMedPubMedCentral Maupin KA, Sinha A, Eugster E, Miller J, Ross J, Paulino V, et al. Glycogene expression alterations associated with pancreatic cancer epithelial-mesenchymal transition in complementary model systems. PLoS One. 2010;5(9):e13002.CrossRefPubMedPubMedCentral
6.
go back to reference Zhang L, Farrell JJ, Zhou H, Elashoff D, Akin D, Park NH, et al. Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. Gastroenterology. 2010;138(3):949–57. e7.CrossRefPubMed Zhang L, Farrell JJ, Zhou H, Elashoff D, Akin D, Park NH, et al. Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. Gastroenterology. 2010;138(3):949–57. e7.CrossRefPubMed
7.
go back to reference Huang M, Tang S-N, Upadhyay G, Marsh JL, Jackman CP, Shankar S, et al. Embelin suppresses growth of human pancreatic cancer xenografts, and pancreatic cancer cells isolated from KrasG12D mice by inhibiting Akt and sonic hedgehog pathways. PLoS One. 2014;9(4):e92161.CrossRefPubMedPubMedCentral Huang M, Tang S-N, Upadhyay G, Marsh JL, Jackman CP, Shankar S, et al. Embelin suppresses growth of human pancreatic cancer xenografts, and pancreatic cancer cells isolated from KrasG12D mice by inhibiting Akt and sonic hedgehog pathways. PLoS One. 2014;9(4):e92161.CrossRefPubMedPubMedCentral
8.
go back to reference Donahue TR, Tran LM, Hill R, Li Y, Kovochich A, Calvopina JH, et al. Integrative survival-based molecular profiling of human pancreatic cancer. Clin Cancer Res. 2012;18(5):1352–63.CrossRefPubMed Donahue TR, Tran LM, Hill R, Li Y, Kovochich A, Calvopina JH, et al. Integrative survival-based molecular profiling of human pancreatic cancer. Clin Cancer Res. 2012;18(5):1352–63.CrossRefPubMed
9.
go back to reference Pang H, Lin A, Holford M, Enerson BE, Lu B, Lawton MP, et al. Pathway analysis using random forests classification and regression. Bioinformatics. 2006;22(16):2028–36.CrossRefPubMed Pang H, Lin A, Holford M, Enerson BE, Lu B, Lawton MP, et al. Pathway analysis using random forests classification and regression. Bioinformatics. 2006;22(16):2028–36.CrossRefPubMed
10.
go back to reference Li Y, Agarwal P, Rajagopalan D. A global pathway crosstalk network. Bioinformatics. 2008;24(12):1442–7.CrossRefPubMed Li Y, Agarwal P, Rajagopalan D. A global pathway crosstalk network. Bioinformatics. 2008;24(12):1442–7.CrossRefPubMed
11.
go back to reference Basu A, Castle VP, Bouziane M, Bhalla K, Haldar S. Crosstalk between extrinsic and intrinsic cell death pathways in pancreatic cancer: synergistic action of estrogen metabolite and ligands of death receptor family. Cancer Res. 2006;66(8):4309–18.CrossRefPubMed Basu A, Castle VP, Bouziane M, Bhalla K, Haldar S. Crosstalk between extrinsic and intrinsic cell death pathways in pancreatic cancer: synergistic action of estrogen metabolite and ligands of death receptor family. Cancer Res. 2006;66(8):4309–18.CrossRefPubMed
13.
go back to reference Maniati E, Bossard M, Cook N, Candido JB, Emami-Shahri N, Nedospasov SA, et al. Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice. J Clin Invest. 2011;121(121):4685–99. 12.CrossRefPubMedPubMedCentral Maniati E, Bossard M, Cook N, Candido JB, Emami-Shahri N, Nedospasov SA, et al. Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice. J Clin Invest. 2011;121(121):4685–99. 12.CrossRefPubMedPubMedCentral
14.
go back to reference Gautier L, Cope L, Bolstad BM, Irizarry RA. affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20(3):307–15.CrossRefPubMed Gautier L, Cope L, Bolstad BM, Irizarry RA. affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20(3):307–15.CrossRefPubMed
15.
go back to reference Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003;4(2):249–64.CrossRefPubMed Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003;4(2):249–64.CrossRefPubMed
16.
go back to reference Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5(10):R80.CrossRefPubMedPubMedCentral Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5(10):R80.CrossRefPubMedPubMedCentral
17.
go back to reference Leek JT. Surrogate variable analysis: University of Washington; 2007 Leek JT. Surrogate variable analysis: University of Washington; 2007
18.
go back to reference Wingender E. The TRANSFAC project as an example of framework technology that supports the analysis of genomic regulation. Brief Bioinform. 2008;9(4):326–32.CrossRefPubMed Wingender E. The TRANSFAC project as an example of framework technology that supports the analysis of genomic regulation. Brief Bioinform. 2008;9(4):326–32.CrossRefPubMed
19.
go back to reference Dennis Jr G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, et al. DAVID: database for annotation, visualization, and integrated discovery. Genome Biol. 2003;4(5):3.CrossRef Dennis Jr G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, et al. DAVID: database for annotation, visualization, and integrated discovery. Genome Biol. 2003;4(5):3.CrossRef
20.
go back to reference Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene Ontology: tool for the unification of biology. Nat Genet. 2000;25(1):25–9.CrossRefPubMedPubMedCentral Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene Ontology: tool for the unification of biology. Nat Genet. 2000;25(1):25–9.CrossRefPubMedPubMedCentral
21.
go back to reference Arakawa K, Kono N, Yamada Y, Mori H, Tomita M. KEGG-based pathway visualization tool for complex omics data. In silico biol. 2005;5(4):419–23.PubMed Arakawa K, Kono N, Yamada Y, Mori H, Tomita M. KEGG-based pathway visualization tool for complex omics data. In silico biol. 2005;5(4):419–23.PubMed
22.
go back to reference Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRING v9. 1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013;41(D1):D808–D15.CrossRefPubMed Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRING v9. 1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013;41(D1):D808–D15.CrossRefPubMed
23.
go back to reference Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.CrossRefPubMedPubMedCentral Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.CrossRefPubMedPubMedCentral
24.
go back to reference Pham L, Christadore L, Schaus S, Kolaczyk ED. Network-based prediction for sources of transcriptional dysregulation using latent pathway identification analysis. Proc Natl Acad Sci. 2011;108(32):13347–52.CrossRefPubMedPubMedCentral Pham L, Christadore L, Schaus S, Kolaczyk ED. Network-based prediction for sources of transcriptional dysregulation using latent pathway identification analysis. Proc Natl Acad Sci. 2011;108(32):13347–52.CrossRefPubMedPubMedCentral
26.
go back to reference Moore F, Santin I, Nogueira TC, Gurzov EN, Marselli L, Marchetti P, et al. The transcription factor C/EBP delta has anti-apoptotic and anti-inflammatory roles in pancreatic beta cells. PLoS One. 2012;7(2):e31062.CrossRefPubMedPubMedCentral Moore F, Santin I, Nogueira TC, Gurzov EN, Marselli L, Marchetti P, et al. The transcription factor C/EBP delta has anti-apoptotic and anti-inflammatory roles in pancreatic beta cells. PLoS One. 2012;7(2):e31062.CrossRefPubMedPubMedCentral
27.
go back to reference Kim JH, Lee JY, Lee KT, Lee JK, Lee KH, Jang K-T, et al. RGS16 and FosB underexpressed in pancreatic cancer with lymph node metastasis promote tumor progression. Tumor Biol. 2010;31(5):541–8.CrossRef Kim JH, Lee JY, Lee KT, Lee JK, Lee KH, Jang K-T, et al. RGS16 and FosB underexpressed in pancreatic cancer with lymph node metastasis promote tumor progression. Tumor Biol. 2010;31(5):541–8.CrossRef
28.
go back to reference Guweidhi A, Kleeff J, Giese N, El Fitori J, Ketterer K, Giese T, et al. Enhanced expression of 14-3-3sigma in pancreatic cancer and its role in cell cycle regulation and apoptosis. Carcinogenesis. 2004;25(9):1575–85.CrossRefPubMed Guweidhi A, Kleeff J, Giese N, El Fitori J, Ketterer K, Giese T, et al. Enhanced expression of 14-3-3sigma in pancreatic cancer and its role in cell cycle regulation and apoptosis. Carcinogenesis. 2004;25(9):1575–85.CrossRefPubMed
29.
go back to reference Mori A, Moser C, Lang SA, Hackl C, Gottfried E, Kreutz M, et al. Up-regulation of Kruppel-like factor 5 in pancreatic cancer is promoted by interleukin-1beta signaling and hypoxia-inducible factor-1alpha. Mol Cancer Res : MCR. 2009;7(8):1390–8. doi:10.1158/1541-7786.mcr-08-0525.CrossRefPubMed Mori A, Moser C, Lang SA, Hackl C, Gottfried E, Kreutz M, et al. Up-regulation of Kruppel-like factor 5 in pancreatic cancer is promoted by interleukin-1beta signaling and hypoxia-inducible factor-1alpha. Mol Cancer Res : MCR. 2009;7(8):1390–8. doi:10.​1158/​1541-7786.​mcr-08-0525.CrossRefPubMed
30.
go back to reference Locatelli M, Ferrero S, Martinelli Boneschi F, Boiocchi L, Zavanone M, Maria Gaini S, et al. The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas. J Neuroimmunol. 2013;260(1):99–106.CrossRefPubMed Locatelli M, Ferrero S, Martinelli Boneschi F, Boiocchi L, Zavanone M, Maria Gaini S, et al. The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas. J Neuroimmunol. 2013;260(1):99–106.CrossRefPubMed
31.
go back to reference Lee S-O, Abdelrahim M, Yoon K, Chintharlapalli S, Papineni S, Kim K, et al. Inactivation of the orphan nuclear receptor TR3/Nur77 inhibits pancreatic cancer cell and tumor growth. Cancer Res. 2010;70(17):6824–36.CrossRefPubMedPubMedCentral Lee S-O, Abdelrahim M, Yoon K, Chintharlapalli S, Papineni S, Kim K, et al. Inactivation of the orphan nuclear receptor TR3/Nur77 inhibits pancreatic cancer cell and tumor growth. Cancer Res. 2010;70(17):6824–36.CrossRefPubMedPubMedCentral
32.
go back to reference Guerra C, Schuhmacher AJ, Cañamero M, Grippo PJ, Verdaguer L, Pérez-Gallego L, et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell. 2007;11(3):291–302.CrossRefPubMed Guerra C, Schuhmacher AJ, Cañamero M, Grippo PJ, Verdaguer L, Pérez-Gallego L, et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell. 2007;11(3):291–302.CrossRefPubMed
33.
go back to reference Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, et al. EMT and dissemination precede pancreatic tumor formation. Cell. 2012;148(1):349–61.CrossRefPubMedPubMedCentral Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, et al. EMT and dissemination precede pancreatic tumor formation. Cell. 2012;148(1):349–61.CrossRefPubMedPubMedCentral
34.
go back to reference Dima SO, Tanase C, Albulescu R, Herlea V, Chivu-Economescu M, Purnichescu-Purtan R, et al. An exploratory study of inflammatory cytokines as prognostic biomarkers in patients with ductal pancreatic adenocarcinoma. Pancreas. 2012;41(7):1001–7.CrossRefPubMed Dima SO, Tanase C, Albulescu R, Herlea V, Chivu-Economescu M, Purnichescu-Purtan R, et al. An exploratory study of inflammatory cytokines as prognostic biomarkers in patients with ductal pancreatic adenocarcinoma. Pancreas. 2012;41(7):1001–7.CrossRefPubMed
35.
36.
go back to reference Rincon M. Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol. 2012;33(11):571–7.CrossRefPubMed Rincon M. Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol. 2012;33(11):571–7.CrossRefPubMed
37.
go back to reference Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, Klöppel G, et al. Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell. 2011;19(4):456–69.CrossRefPubMed Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, Klöppel G, et al. Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell. 2011;19(4):456–69.CrossRefPubMed
38.
go back to reference Guan J, Zhang H, Wen Z, Gu Y, Cheng Y, Sun Y et al. Retinoic acid inhibits pancreatic cancer cell migration and EMT through the downregulation of IL-6 in cancer associated fibroblast cells. Cancer letters. 2013. Guan J, Zhang H, Wen Z, Gu Y, Cheng Y, Sun Y et al. Retinoic acid inhibits pancreatic cancer cell migration and EMT through the downregulation of IL-6 in cancer associated fibroblast cells. Cancer letters. 2013.
39.
go back to reference Hong DS, Angelo LS, Kurzrock R. Interleukin‐6 and its receptor in cancer. Cancer. 2007;110(9):1911–28.CrossRefPubMed Hong DS, Angelo LS, Kurzrock R. Interleukin‐6 and its receptor in cancer. Cancer. 2007;110(9):1911–28.CrossRefPubMed
40.
go back to reference Song J, Singh M. How and when should interactome-derived clusters be used to predict functional modules and protein function? Bioinformatics. 2009;25(23):3143–50.CrossRefPubMedPubMedCentral Song J, Singh M. How and when should interactome-derived clusters be used to predict functional modules and protein function? Bioinformatics. 2009;25(23):3143–50.CrossRefPubMedPubMedCentral
41.
go back to reference Fukata M, Vamadevan AS, Abreu MT, editors. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders. Seminars in immunology; 2009: Elsevier. Fukata M, Vamadevan AS, Abreu MT, editors. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders. Seminars in immunology; 2009: Elsevier.
42.
go back to reference Huzarski T, Lener M, Domagała W, Gronwald J, Byrski T, Kurzawski G, et al. The 3020insC allele of NOD2 predisposes to early-onset breast cancer. Breast Cancer Res Treat. 2005;89(1):91–3.CrossRefPubMed Huzarski T, Lener M, Domagała W, Gronwald J, Byrski T, Kurzawski G, et al. The 3020insC allele of NOD2 predisposes to early-onset breast cancer. Breast Cancer Res Treat. 2005;89(1):91–3.CrossRefPubMed
43.
go back to reference Papaconstantinou I, Theodoropoulos G, Gazouli M, Panoussopoulos D, Mantzaris GJ, Felekouras E, et al. Association between mutations in the CARD15/NOD2 gene and colorectal cancer in a Greek population. Int J Cancer. 2005;114(3):433–5.CrossRefPubMed Papaconstantinou I, Theodoropoulos G, Gazouli M, Panoussopoulos D, Mantzaris GJ, Felekouras E, et al. Association between mutations in the CARD15/NOD2 gene and colorectal cancer in a Greek population. Int J Cancer. 2005;114(3):433–5.CrossRefPubMed
44.
go back to reference Tsuji M, Suzuki K, Kinoshita K, Fagarasan S, editors. Dynamic interactions between bacteria and immune cells leading to intestinal IgA synthesis. Seminars in immunology; 2008: Elsevier. Tsuji M, Suzuki K, Kinoshita K, Fagarasan S, editors. Dynamic interactions between bacteria and immune cells leading to intestinal IgA synthesis. Seminars in immunology; 2008: Elsevier.
46.
go back to reference Park J-H, Kim Y-G, McDonald C, Kanneganti T-D, Hasegawa M, Body-Malapel M, et al. RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. J Immunol. 2007;178(4):2380–6.CrossRefPubMed Park J-H, Kim Y-G, McDonald C, Kanneganti T-D, Hasegawa M, Body-Malapel M, et al. RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. J Immunol. 2007;178(4):2380–6.CrossRefPubMed
Metadata
Title
RETRACTED ARTICLE: A comprehensive analysis of candidate genes and pathways in pancreatic cancer
Authors
Jie Liu
Jun Li
Hali Li
Aidong Li
Biou Liu
Liou Han
Publication date
01-03-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2787-y

Other articles of this Issue 3/2015

Tumor Biology 3/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine