Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 2/2018

29.12.2017 | Original Article – Cancer Research

Identification of genes highly downregulated in pancreatic cancer through a meta-analysis of microarray datasets: implications for discovery of novel tumor-suppressor genes and therapeutic targets

verfasst von: Nalin C. W. Goonesekere, Wyatt Andersen, Alex Smith, Xiaosheng Wang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a 5-year survival rate of about 7%. Recent failures of targeted therapies inhibiting kinase activity in clinical trials have highlighted the need for new approaches towards combating this deadly disease.

Methods

In this study, we have identified genes that are significantly downregulated in PC, through a meta-analysis of large number of microarray datasets. We have used qRT-PCR to confirm the downregulation of selected genes in a panel of PC cell lines.

Results

This study has yielded several novel candidate tumor-suppressor genes (TSGs) including GNMT, CEL, PLA2G1B and SERPINI2. We highlight the role of GNMT, a methyl transferase associated with the methylation potential of the cell, and CEL, a lipase, as potential therapeutic targets. We have uncovered genetic links to risk factors associated with PC such as smoking and obesity. Genes important for patient survival and prognosis are also discussed, and we confirm the dysregulation of metabolic pathways previously observed in PC.

Conclusions

While many of the genes downregulated in our dataset are associated with protein products normally produced by the pancreas for excretion, we have uncovered some genes whose downregulation appear to play a more causal role in PC. These genes will assist in providing a better understanding of the disease etiology of PC, and in the search for new therapeutic targets and biomarkers.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
Zurück zum Zitat Abbenhardt C, Poole EM, Kulmacz RJ et al (2013) Phospholipase A2G1B polymorphisms and risk of colorectal neoplasia. Int J Mol Epidemiol Genet 4:140–149PubMedPubMedCentral Abbenhardt C, Poole EM, Kulmacz RJ et al (2013) Phospholipase A2G1B polymorphisms and risk of colorectal neoplasia. Int J Mol Epidemiol Genet 4:140–149PubMedPubMedCentral
Zurück zum Zitat Apte MV, Wilson JS, Lugea A et al (2013) A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology 144:1210–1219CrossRefPubMedPubMedCentral Apte MV, Wilson JS, Lugea A et al (2013) A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology 144:1210–1219CrossRefPubMedPubMedCentral
Zurück zum Zitat Bailey P, Chang DK, Nones K et al (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531:47–52CrossRefPubMed Bailey P, Chang DK, Nones K et al (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531:47–52CrossRefPubMed
Zurück zum Zitat Bhasin MK, Ndebele K, Bucur O et al (2016) Meta-analysis of transcriptome data identifies a novel 5-gene pancreatic adenocarcinoma classifier. Oncotarget 7:23263–23281CrossRefPubMedPubMedCentral Bhasin MK, Ndebele K, Bucur O et al (2016) Meta-analysis of transcriptome data identifies a novel 5-gene pancreatic adenocarcinoma classifier. Oncotarget 7:23263–23281CrossRefPubMedPubMedCentral
Zurück zum Zitat Bochkis IM, Rubins NE, White P et al (2008) Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress. Nat Med 14:828–836CrossRefPubMedPubMedCentral Bochkis IM, Rubins NE, White P et al (2008) Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress. Nat Med 14:828–836CrossRefPubMedPubMedCentral
Zurück zum Zitat Breitling R, Armengaud P, Amtmann A et al (2004) Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS Lett 573:83–92CrossRefPubMed Breitling R, Armengaud P, Amtmann A et al (2004) Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS Lett 573:83–92CrossRefPubMed
Zurück zum Zitat Chiaradonna F, Gaglio D, Vanoni M et al (2006) Expression of transforming K-Ras oncogene affects mitochondrial function and morphology in mouse fibroblasts. Biochim Biophys Acta 1757:1338–1356CrossRefPubMed Chiaradonna F, Gaglio D, Vanoni M et al (2006) Expression of transforming K-Ras oncogene affects mitochondrial function and morphology in mouse fibroblasts. Biochim Biophys Acta 1757:1338–1356CrossRefPubMed
Zurück zum Zitat Collisson EA, Sadanandam A, Olson P et al (2011) Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med 17:500–503CrossRefPubMedPubMedCentral Collisson EA, Sadanandam A, Olson P et al (2011) Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med 17:500–503CrossRefPubMedPubMedCentral
Zurück zum Zitat Cook WD, McCaw BJ (2000) Accommodating haploinsufficient tumor suppressor genes in Knudson’s model. Oncogene 19:3434–3438CrossRefPubMed Cook WD, McCaw BJ (2000) Accommodating haploinsufficient tumor suppressor genes in Knudson’s model. Oncogene 19:3434–3438CrossRefPubMed
Zurück zum Zitat Dal Molin M, Zhang M, de Wilde RF et al (2015) Very long-term survival following resection for pancreatic cancer is not explained by commonly mutated genes: results of whole-exome sequencing analysis. Clin Cancer Res 21:1944–1950CrossRefPubMed Dal Molin M, Zhang M, de Wilde RF et al (2015) Very long-term survival following resection for pancreatic cancer is not explained by commonly mutated genes: results of whole-exome sequencing analysis. Clin Cancer Res 21:1944–1950CrossRefPubMed
Zurück zum Zitat Davidson SM, Jonas O, Keibler MA et al (2017) Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors. Nat Med 23:235–241CrossRefPubMed Davidson SM, Jonas O, Keibler MA et al (2017) Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors. Nat Med 23:235–241CrossRefPubMed
Zurück zum Zitat Delitto D, Delitto AE, DiVita BB et al (2017) Human pancreatic cancer cells induce a MyD88-dependent stromal response to promote a tumor-tolerant immune microenvironment. Cancer Res 77:672–683CrossRefPubMed Delitto D, Delitto AE, DiVita BB et al (2017) Human pancreatic cancer cells induce a MyD88-dependent stromal response to promote a tumor-tolerant immune microenvironment. Cancer Res 77:672–683CrossRefPubMed
Zurück zum Zitat Fabregat A, Sidiropoulos K, Garapati P et al (2016) The reactome pathway knowledgebase. Nucleic Acids Res 44:D481–D487CrossRefPubMed Fabregat A, Sidiropoulos K, Garapati P et al (2016) The reactome pathway knowledgebase. Nucleic Acids Res 44:D481–D487CrossRefPubMed
Zurück zum Zitat Fajans SS, Bell GI, Polonsky KS (2001) Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med 345:971–980CrossRefPubMed Fajans SS, Bell GI, Polonsky KS (2001) Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med 345:971–980CrossRefPubMed
Zurück zum Zitat Fleming JB, Gonzalez RJ, Petzel MQ et al (2009) Influence of obesity on cancer-related outcomes after pancreatectomy to treat pancreatic adenocarcinoma. Arch Surg 144:216–221CrossRefPubMed Fleming JB, Gonzalez RJ, Petzel MQ et al (2009) Influence of obesity on cancer-related outcomes after pancreatectomy to treat pancreatic adenocarcinoma. Arch Surg 144:216–221CrossRefPubMed
Zurück zum Zitat Fukushige S, Horii A (2014) Road to early detection of pancreatic cancer: attempts to utilize epigenetic biomarkers. Cancer Lett 342:231–237CrossRefPubMed Fukushige S, Horii A (2014) Road to early detection of pancreatic cancer: attempts to utilize epigenetic biomarkers. Cancer Lett 342:231–237CrossRefPubMed
Zurück zum Zitat Goonesekere NC, Wang X, Ludwig L et al (2014) A meta analysis of pancreatic microarray datasets yields new targets as cancer genes and biomarkers. PLoS One 9:e93046CrossRefPubMedPubMedCentral Goonesekere NC, Wang X, Ludwig L et al (2014) A meta analysis of pancreatic microarray datasets yields new targets as cancer genes and biomarkers. PLoS One 9:e93046CrossRefPubMedPubMedCentral
Zurück zum Zitat Harris NL, Vennin C, Conway JR et al (2017) SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer. Oncogene 36:4288–4298CrossRefPubMedPubMedCentral Harris NL, Vennin C, Conway JR et al (2017) SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer. Oncogene 36:4288–4298CrossRefPubMedPubMedCentral
Zurück zum Zitat Heit C, Jackson BC, McAndrews M et al (2013) Update of the human and mouse SERPIN gene superfamily. Hum Genom 7:22CrossRef Heit C, Jackson BC, McAndrews M et al (2013) Update of the human and mouse SERPIN gene superfamily. Hum Genom 7:22CrossRef
Zurück zum Zitat Higgins WJ, Grehan GT, Wynne KJ et al (2017) SerpinI2 (pancpin) is an inhibitory serpin targeting pancreatic elastase and chymotrypsin. Biochim Biophys Acta 1865:195–200CrossRefPubMed Higgins WJ, Grehan GT, Wynne KJ et al (2017) SerpinI2 (pancpin) is an inhibitory serpin targeting pancreatic elastase and chymotrypsin. Biochim Biophys Acta 1865:195–200CrossRefPubMed
Zurück zum Zitat Hong F, Breitling R (2008) A comparison of meta-analysis methods for detecting differentially expressed genes in microarray experiments. Bioinformatics 24:374–382CrossRefPubMed Hong F, Breitling R (2008) A comparison of meta-analysis methods for detecting differentially expressed genes in microarray experiments. Bioinformatics 24:374–382CrossRefPubMed
Zurück zum Zitat Hong F, Breitling R, McEntee CW et al (2006) RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics 22:2825–2827CrossRefPubMed Hong F, Breitling R, McEntee CW et al (2006) RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics 22:2825–2827CrossRefPubMed
Zurück zum Zitat Irizarry RA, Warren D, Spencer F et al (2005) Multiple-laboratory comparison of microarray platforms. Nat Method 2:345–350CrossRef Irizarry RA, Warren D, Spencer F et al (2005) Multiple-laboratory comparison of microarray platforms. Nat Method 2:345–350CrossRef
Zurück zum Zitat Iyer NV, Kotch LE, Agani F et al (1998) Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 12:149–162CrossRefPubMedPubMedCentral Iyer NV, Kotch LE, Agani F et al (1998) Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 12:149–162CrossRefPubMedPubMedCentral
Zurück zum Zitat Jain R, Fischer S, Serra S et al (2010) The use of Cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. Appl Immunohistochem Mol Morphol 18:9–15CrossRefPubMed Jain R, Fischer S, Serra S et al (2010) The use of Cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. Appl Immunohistochem Mol Morphol 18:9–15CrossRefPubMed
Zurück zum Zitat Jiang H, Hu H, Tong X et al (2012) Calcium-binding protein S100P and cancer: mechanisms and clinical relevance. J Cancer Res Clin Oncol 138:1–9CrossRefPubMed Jiang H, Hu H, Tong X et al (2012) Calcium-binding protein S100P and cancer: mechanisms and clinical relevance. J Cancer Res Clin Oncol 138:1–9CrossRefPubMed
Zurück zum Zitat Kant R, Yen CH, Lu CK et al (2016) Identification of 1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranoside as a Glycine N-Methyltransferase enhancer by high-throughput screening of natural products inhibits hepatocellular carcinoma. Int J Mol Sci 17:669CrossRefPubMedCentral Kant R, Yen CH, Lu CK et al (2016) Identification of 1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranoside as a Glycine N-Methyltransferase enhancer by high-throughput screening of natural products inhibits hepatocellular carcinoma. Int J Mol Sci 17:669CrossRefPubMedCentral
Zurück zum Zitat Kleeff J, Michl P (2017) Targeted therapy of pancreatic cancer: biomarkers are needed. Lancet Oncol 421–422 Kleeff J, Michl P (2017) Targeted therapy of pancreatic cancer: biomarkers are needed. Lancet Oncol 421–422
Zurück zum Zitat Lee DD, Seung HS (1999) Learning the parts of objects by non-negative matrix factorization. Nature 401:788–791CrossRefPubMed Lee DD, Seung HS (1999) Learning the parts of objects by non-negative matrix factorization. Nature 401:788–791CrossRefPubMed
Zurück zum Zitat Li CH, Yen CH, Chen YF et al (2017) Characterization of the GNMT-HectH9-PREX2 tripartite relationship in the pathogenesis of hepatocellular carcinoma. Int J Cancer 140:2284–2297CrossRefPubMed Li CH, Yen CH, Chen YF et al (2017) Characterization of the GNMT-HectH9-PREX2 tripartite relationship in the pathogenesis of hepatocellular carcinoma. Int J Cancer 140:2284–2297CrossRefPubMed
Zurück zum Zitat Liu Y, Ni R, Zhang H et al (2016) Identification of feature genes for smoking-related lung adenocarcinoma based on gene expression profile data. Onco Target Ther 9:7397–7407CrossRef Liu Y, Ni R, Zhang H et al (2016) Identification of feature genes for smoking-related lung adenocarcinoma based on gene expression profile data. Onco Target Ther 9:7397–7407CrossRef
Zurück zum Zitat Makohon-Moore A, Iacobuzio-Donahue CA (2016) Pancreatic cancer biology and genetics from an evolutionary perspective. Nat Rev Cancer 16:553–565CrossRefPubMedPubMedCentral Makohon-Moore A, Iacobuzio-Donahue CA (2016) Pancreatic cancer biology and genetics from an evolutionary perspective. Nat Rev Cancer 16:553–565CrossRefPubMedPubMedCentral
Zurück zum Zitat Malvezzi M, Carioli G, Bertuccio P et al (2016) European cancer mortality predictions for the year 2016 with focus on leukaemias. Ann Oncol 27:725–731CrossRefPubMed Malvezzi M, Carioli G, Bertuccio P et al (2016) European cancer mortality predictions for the year 2016 with focus on leukaemias. Ann Oncol 27:725–731CrossRefPubMed
Zurück zum Zitat Martínez-Chantar ML, Vázquez-Chantada M, Ariz U et al (2008) Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology 47:1191–1199CrossRefPubMed Martínez-Chantar ML, Vázquez-Chantada M, Ariz U et al (2008) Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology 47:1191–1199CrossRefPubMed
Zurück zum Zitat Mi H, Muruganujan A, Casagrande JT et al (2013) Large-scale gene function analysis with the PANTHER classification system. Nat Protoc 8:1551–1566CrossRefPubMed Mi H, Muruganujan A, Casagrande JT et al (2013) Large-scale gene function analysis with the PANTHER classification system. Nat Protoc 8:1551–1566CrossRefPubMed
Zurück zum Zitat Middleton G, Palmer DH, Greenhalf W et al (2017) Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial. Lancet Oncol 18:486–499CrossRefPubMed Middleton G, Palmer DH, Greenhalf W et al (2017) Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial. Lancet Oncol 18:486–499CrossRefPubMed
Zurück zum Zitat Moffitt RA, Marayati R, Flate EL et al (2015) Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet 47:1168–1178CrossRefPubMedPubMedCentral Moffitt RA, Marayati R, Flate EL et al (2015) Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet 47:1168–1178CrossRefPubMedPubMedCentral
Zurück zum Zitat Morris LG, Chan TA (2015) Therapeutic targeting of tumor suppressor genes. Cancer 121:1357–1368CrossRefPubMed Morris LG, Chan TA (2015) Therapeutic targeting of tumor suppressor genes. Cancer 121:1357–1368CrossRefPubMed
Zurück zum Zitat Nakae J, Biggs WH, Kitamura T et al (2002) Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet 32:245–253CrossRefPubMed Nakae J, Biggs WH, Kitamura T et al (2002) Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet 32:245–253CrossRefPubMed
Zurück zum Zitat Notta F, Chan-Seng-Yue M, Lemire M et al (2016) A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns. Nature 538:378–382CrossRefPubMedPubMedCentral Notta F, Chan-Seng-Yue M, Lemire M et al (2016) A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns. Nature 538:378–382CrossRefPubMedPubMedCentral
Zurück zum Zitat Olivares O, Mayers JR, Gouirand V et al (2017) Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nat Commun 8:16031CrossRefPubMedPubMedCentral Olivares O, Mayers JR, Gouirand V et al (2017) Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nat Commun 8:16031CrossRefPubMedPubMedCentral
Zurück zum Zitat Ozaki K, Nagata M, Suzuki M et al (1998) Isolation and characterization of a novel human pancreas-specific gene, pancpin, that is down-regulated in pancreatic cancer cells. Genes Chromosom Cancer 22:179–185CrossRefPubMed Ozaki K, Nagata M, Suzuki M et al (1998) Isolation and characterization of a novel human pancreas-specific gene, pancpin, that is down-regulated in pancreatic cancer cells. Genes Chromosom Cancer 22:179–185CrossRefPubMed
Zurück zum Zitat Pannala R, Basu A, Petersen GM et al (2009) New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol 10:88–95CrossRefPubMedPubMedCentral Pannala R, Basu A, Petersen GM et al (2009) New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol 10:88–95CrossRefPubMedPubMedCentral
Zurück zum Zitat Pechalrieu D, Etievant C, Arimondo PB (2017) DNA methyltransferase inhibitors in cancer: from pharmacology to translational studies. Biochem Pharmacol 129:1–13CrossRefPubMed Pechalrieu D, Etievant C, Arimondo PB (2017) DNA methyltransferase inhibitors in cancer: from pharmacology to translational studies. Biochem Pharmacol 129:1–13CrossRefPubMed
Zurück zum Zitat Piekarz RL, Frye R, Turner M et al (2009) Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27:5410–5417CrossRefPubMedPubMedCentral Piekarz RL, Frye R, Turner M et al (2009) Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27:5410–5417CrossRefPubMedPubMedCentral
Zurück zum Zitat Provenzano PP, Eliceiri KW, Campbell JM et al (2006) Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med 4:38CrossRefPubMedPubMedCentral Provenzano PP, Eliceiri KW, Campbell JM et al (2006) Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med 4:38CrossRefPubMedPubMedCentral
Zurück zum Zitat Rahib L, Smith BD, Aizenberg R et al (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74:2913–2921CrossRefPubMed Rahib L, Smith BD, Aizenberg R et al (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74:2913–2921CrossRefPubMed
Zurück zum Zitat Rhodes DR, Kalyana-Sundaram S, Mahavisno V et al (2007) Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. NEO 9:166–180CrossRef Rhodes DR, Kalyana-Sundaram S, Mahavisno V et al (2007) Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. NEO 9:166–180CrossRef
Zurück zum Zitat Shen J, Tsoi H, Liang Q et al (2016) Oncogenic mutations and dysregulated pathways in obesity-associated hepatocellular carcinoma. Oncogene 35:6271–6280CrossRefPubMedPubMedCentral Shen J, Tsoi H, Liang Q et al (2016) Oncogenic mutations and dysregulated pathways in obesity-associated hepatocellular carcinoma. Oncogene 35:6271–6280CrossRefPubMedPubMedCentral
Zurück zum Zitat Smid M, Dorssers LCJ, Jenster G (2003) Venn Mapping: clustering of heterologous microarray data based on the number of co-occurring differentially expressed genes. Bioinformatics 19:2065–2071CrossRefPubMed Smid M, Dorssers LCJ, Jenster G (2003) Venn Mapping: clustering of heterologous microarray data based on the number of co-occurring differentially expressed genes. Bioinformatics 19:2065–2071CrossRefPubMed
Zurück zum Zitat Smith A, Poole L, Dhanwada K et al (2016) Identification of candidate biomarkers and cancer genes AHNAK2 and EPPK1 in pancreatic cancer. Brit J Med Med Rep 18:1–8CrossRef Smith A, Poole L, Dhanwada K et al (2016) Identification of candidate biomarkers and cancer genes AHNAK2 and EPPK1 in pancreatic cancer. Brit J Med Med Rep 18:1–8CrossRef
Zurück zum Zitat Stark C, Breitkreutz BJ, Reguly T et al (2006) BioGRID: a general repository for interaction datasets. Nucleic Acids Res 34:D535–D539CrossRefPubMed Stark C, Breitkreutz BJ, Reguly T et al (2006) BioGRID: a general repository for interaction datasets. Nucleic Acids Res 34:D535–D539CrossRefPubMed
Zurück zum Zitat Subramanian A, Tamayo P, Mootha VK et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545–15550CrossRefPubMedPubMedCentral Subramanian A, Tamayo P, Mootha VK et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545–15550CrossRefPubMedPubMedCentral
Zurück zum Zitat Tanaka M, Shibahara J, Fukushima N et al (2011) Claudin-18 is an early-stage marker of pancreatic carcinogenesis. J Histochem Cytochem 59:942–952CrossRefPubMedPubMedCentral Tanaka M, Shibahara J, Fukushima N et al (2011) Claudin-18 is an early-stage marker of pancreatic carcinogenesis. J Histochem Cytochem 59:942–952CrossRefPubMedPubMedCentral
Zurück zum Zitat Thompson MJ, Rubbi L, Dawson DW et al (2015) Pancreatic cancer patient survival correlates with DNA methylation of pancreas development genes. PLoS One 10:e0128814CrossRefPubMedPubMedCentral Thompson MJ, Rubbi L, Dawson DW et al (2015) Pancreatic cancer patient survival correlates with DNA methylation of pancreas development genes. PLoS One 10:e0128814CrossRefPubMedPubMedCentral
Zurück zum Zitat Vorvis C, Hatziapostolou M, Mahurkar-Joshi S et al (2016) Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer. Am J Physiol Gastrointest Liver Physiol 310:G1124–G1137CrossRefPubMedPubMedCentral Vorvis C, Hatziapostolou M, Mahurkar-Joshi S et al (2016) Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer. Am J Physiol Gastrointest Liver Physiol 310:G1124–G1137CrossRefPubMedPubMedCentral
Zurück zum Zitat Wu P, Nielsen TE, Clausen MH (2016) Small-molecule kinase inhibitors: an analysis of FDA-approved drugs. Drug Discov Today 21:5–10CrossRefPubMed Wu P, Nielsen TE, Clausen MH (2016) Small-molecule kinase inhibitors: an analysis of FDA-approved drugs. Drug Discov Today 21:5–10CrossRefPubMed
Zurück zum Zitat Yachida S, Iacobuzio-Donahue CA (2009) The pathology and genetics of metastatic pancreatic cancer. Arch Pathol Lab Med 133:413–422PubMed Yachida S, Iacobuzio-Donahue CA (2009) The pathology and genetics of metastatic pancreatic cancer. Arch Pathol Lab Med 133:413–422PubMed
Zurück zum Zitat Yachida S, Jones S, Bozic I et al (2010) Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467:1114–1117CrossRefPubMedPubMedCentral Yachida S, Jones S, Bozic I et al (2010) Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467:1114–1117CrossRefPubMedPubMedCentral
Zurück zum Zitat Yen CH, Lu YC, Li CH et al (2012) Functional characterization of glycine N-methyltransferase and its interactive protein DEPDC6/DEPTOR in hepatocellular carcinoma. Mol Med 18:286–296CrossRefPubMed Yen CH, Lu YC, Li CH et al (2012) Functional characterization of glycine N-methyltransferase and its interactive protein DEPDC6/DEPTOR in hepatocellular carcinoma. Mol Med 18:286–296CrossRefPubMed
Zurück zum Zitat Yonezawa S, Higashi M, Yamada N et al (2011) Mucins in human neoplasms: clinical pathology, gene expression and diagnostic application. Pathol Int 61:697–716CrossRefPubMed Yonezawa S, Higashi M, Yamada N et al (2011) Mucins in human neoplasms: clinical pathology, gene expression and diagnostic application. Pathol Int 61:697–716CrossRefPubMed
Zurück zum Zitat Yoshihara K, Shahmoradgoli M, Martínez E et al (2013) Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun 4:2612CrossRefPubMedPubMedCentral Yoshihara K, Shahmoradgoli M, Martínez E et al (2013) Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun 4:2612CrossRefPubMedPubMedCentral
Zurück zum Zitat Zhan HX, Zhou B, Cheng YG et al (2017) Crosstalk between stromal cells and cancer cells in pancreatic cancer: new insights into stromal biology. Cancer Lett 392:83–93CrossRefPubMed Zhan HX, Zhou B, Cheng YG et al (2017) Crosstalk between stromal cells and cancer cells in pancreatic cancer: new insights into stromal biology. Cancer Lett 392:83–93CrossRefPubMed
Zurück zum Zitat Zhang G, He P, Tan H et al (2013) Integration of metabolomics and transcriptomics revealed a fatty acid network exerting growth inhibitory effects in human pancreatic cancer. Clin Cancer Res 19:4983–4993CrossRefPubMedPubMedCentral Zhang G, He P, Tan H et al (2013) Integration of metabolomics and transcriptomics revealed a fatty acid network exerting growth inhibitory effects in human pancreatic cancer. Clin Cancer Res 19:4983–4993CrossRefPubMedPubMedCentral
Zurück zum Zitat Zyromski NJ, Mathur A, Pitt HA et al (2009) Obesity potentiates the growth and dissemination of pancreatic cancer. Surgery 146:258–263CrossRefPubMed Zyromski NJ, Mathur A, Pitt HA et al (2009) Obesity potentiates the growth and dissemination of pancreatic cancer. Surgery 146:258–263CrossRefPubMed
Metadaten
Titel
Identification of genes highly downregulated in pancreatic cancer through a meta-analysis of microarray datasets: implications for discovery of novel tumor-suppressor genes and therapeutic targets
verfasst von
Nalin C. W. Goonesekere
Wyatt Andersen
Alex Smith
Xiaosheng Wang
Publikationsdatum
29.12.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2018
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-017-2558-4

Weitere Artikel der Ausgabe 2/2018

Journal of Cancer Research and Clinical Oncology 2/2018 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.