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Published in: World Journal of Surgery 3/2005

01-03-2005 | Symposium

Gene Overexpression in Pancreatic Adenocarcinoma: Diagnostic and Therapeutic Implications

Authors: Joel A. Rodriguez, B.A., Min Li, Ph.D., Qizhi Yao, M.D., Ph.D., Changyi Chen, M.D., Ph.D., William E. Fisher, M.D.

Published in: World Journal of Surgery | Issue 3/2005

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Abstract

Pancreatic cancer is the deadliest of cancers, and effective diagnostic and therapeutic strategies are lacking. Global gene expression profiling holds promise for improved diagnosis and treatment. Knowledge of the location and timing of gene overexpression and the function of these genes, including their effects on signaling pathways, is important. These data may be used to develop histologic and serum biomarkers as well as to develop immunotherapeutic, molecular targeting, and gene therapy strategies. We have compiled a list of overexpressed genes in pancreatic cancer for which overexpression was confirmed by reverse transcriptase polymerase chain reaction, immunohistochemistry, and/or in situ hybridization following initial identification by global gene expression profiling. The techniques used in the determination of overexpression, problems encountered in global gene expression profiling, and the diagnostic and therapeutic implications of overexpression are discussed. The S100 gene family, mesothelin, prostate stem cell antigen, and 14-3-3 sigma, may have important clinical implications in pancreatic cancer diagnosis and treatment.
Literature
1.
go back to reference Jemal, A, Murray, T, Samuels, A, et al. 2003Cancer statistics, 2003CA Cancer J. Clin.53526PubMed Jemal, A, Murray, T, Samuels, A,  et al. 2003Cancer statistics, 2003CA Cancer J. Clin.53526PubMed
2.
go back to reference Velculescu, VE, Zhang, L, Vogelstein, B, et al. 1995Serial analysis of gene expressionScience270484487PubMed Velculescu, VE, Zhang, L, Vogelstein, B,  et al. 1995Serial analysis of gene expressionScience270484487PubMed
3.
go back to reference Brown, PO, Botstein, D 1999Exploring the new world of the genome with DNA microarraysNat. Genet.213337CrossRefPubMed Brown, PO, Botstein, D 1999Exploring the new world of the genome with DNA microarraysNat. Genet.213337CrossRefPubMed
5.
go back to reference Crnogorac-Jurcevic, T, Missiaglia, E, Blaveri, E, et al. 2003Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalentJ. Pathol.2016374CrossRefPubMed Crnogorac-Jurcevic, T, Missiaglia, E, Blaveri, E,  et al. 2003Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalentJ. Pathol.2016374CrossRefPubMed
6.
go back to reference Logsdon, CD, Simeone, DM, Binkley, C, et al. 2003Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancerCancer Res.6326492657PubMed Logsdon, CD, Simeone, DM, Binkley, C,  et al. 2003Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancerCancer Res.6326492657PubMed
7.
go back to reference Crnogorac-Jurcevic, T, Efthimiou, E, Capelli, P, et al. 2001Gene expression profiles of pancreatic cancer and stromal desmoplasiaOncogene2074377446CrossRefPubMed Crnogorac-Jurcevic, T, Efthimiou, E, Capelli, P,  et al. 2001Gene expression profiles of pancreatic cancer and stromal desmoplasiaOncogene2074377446CrossRefPubMed
8.
go back to reference Crnogorac-Jurcevic, T, Efthimiou, E, Nielsen, T, et al. 2002Expression profiling of microdissected pancreatic adenocarcinomasOncogene2145874594CrossRefPubMed Crnogorac-Jurcevic, T, Efthimiou, E, Nielsen, T,  et al. 2002Expression profiling of microdissected pancreatic adenocarcinomasOncogene2145874594CrossRefPubMed
9.
go back to reference Han, H, Bearss, DJ, Browne, LW, et al. 2002Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarrayCancer Res.6228902896PubMed Han, H, Bearss, DJ, Browne, LW,  et al. 2002Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarrayCancer Res.6228902896PubMed
10.
go back to reference Friess, H, Ding, J, Kleeff, J, et al. 2003Microarray-based identification of differentially expressed growth- and metastasis-associated genes in pancreatic cancerCell. Mol. Life Sci.6011801199PubMed Friess, H, Ding, J, Kleeff, J,  et al. 2003Microarray-based identification of differentially expressed growth- and metastasis-associated genes in pancreatic cancerCell. Mol. Life Sci.6011801199PubMed
11.
go back to reference Rosty, C, Goggins, M 2002Early detection of pancreatic carcinomaHematol. Oncol. Clin. North Am.63752 Rosty, C, Goggins, M 2002Early detection of pancreatic carcinomaHematol. Oncol. Clin. North Am.63752
12.
go back to reference Hruban, RH, Adsay, NV, Albores-Saavedra, J, et al. 2001Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesionsAm. J. Surg. Pathol.25579586CrossRefPubMed Hruban, RH, Adsay, NV, Albores-Saavedra, J,  et al. 2001Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesionsAm. J. Surg. Pathol.25579586CrossRefPubMed
13.
go back to reference Day, JD, Digiuseppe, JA, Yeo, C, et al. 1996Immunohistochemical evaluation of HER-2/neu expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasmsHum Pathol.27119124CrossRefPubMed Day, JD, Digiuseppe, JA, Yeo, C,  et al. 1996Immunohistochemical evaluation of HER-2/neu expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasmsHum Pathol.27119124CrossRefPubMed
14.
go back to reference Hruban, RH, Mansfeld, AD, Offerhaus, GJ, et al. 1993K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridizationAm. J. Pathol.143545554PubMed Hruban, RH, Mansfeld, AD, Offerhaus, GJ,  et al. 1993K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridizationAm. J. Pathol.143545554PubMed
15.
go back to reference Klein, WM, Hruban, RH, Klein-Szanto, AJ, et al. 2002Direct correlation between proliferative activity and dysplasia in pancreatic intraepithelial neoplasia (PanIN): additional evidence for a recently proposed model of progressionMod. Pathol.15441447CrossRefPubMed Klein, WM, Hruban, RH, Klein-Szanto, AJ,  et al. 2002Direct correlation between proliferative activity and dysplasia in pancreatic intraepithelial neoplasia (PanIN): additional evidence for a recently proposed model of progressionMod. Pathol.15441447CrossRefPubMed
16.
go back to reference Terris, B, Blaveri, E, Crnogorac-Jurcevic, T, et al. 2002Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreasAm. J. Pathol.16017451754PubMed Terris, B, Blaveri, E, Crnogorac-Jurcevic, T,  et al. 2002Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreasAm. J. Pathol.16017451754PubMed
17.
go back to reference Iacobuzio-Donahue, CA, Klimstra, DS, Adsay, NV, et al. 2000Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: comparison with conventional ductal adenocarcinomasAm. J. Pathol.157755761PubMed Iacobuzio-Donahue, CA, Klimstra, DS, Adsay, NV,  et al. 2000Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: comparison with conventional ductal adenocarcinomasAm. J. Pathol.157755761PubMed
18.
go back to reference Nakatsura, T, Senju, S, Yamada, K, et al. 2001Gene cloning of immunogenic antigens overexpressed in pancreatic cancerBiochem. Biophys. Res. Commun.281936944PubMed Nakatsura, T, Senju, S, Yamada, K,  et al. 2001Gene cloning of immunogenic antigens overexpressed in pancreatic cancerBiochem. Biophys. Res. Commun.281936944PubMed
19.
go back to reference Nakatsura, T, Senju, S, Ito, M, et al. 2002Cellular and humoral immune responses to a human pancreatic cancer antigen, coactosin-like protein, originally defined by the SEREX methodEur. J. Immunol.32826836PubMed Nakatsura, T, Senju, S, Ito, M,  et al. 2002Cellular and humoral immune responses to a human pancreatic cancer antigen, coactosin-like protein, originally defined by the SEREX methodEur. J. Immunol.32826836PubMed
20.
go back to reference Tarbe, N, Evtimova, V, Burtscher, H, et al. 2001Transcriptional profiling of cell lines derived from an orthotopic pancreatic tumor model reveals metastasis-associated genesAnticancer Res.2132213228PubMed Tarbe, N, Evtimova, V, Burtscher, H,  et al. 2001Transcriptional profiling of cell lines derived from an orthotopic pancreatic tumor model reveals metastasis-associated genesAnticancer Res.2132213228PubMed
21.
go back to reference Scala, S, Portella, G, Fedele, M, et al. 2000Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasiasProc. Natl. Acad. Sci. USA9742564261PubMed Scala, S, Portella, G, Fedele, M,  et al. 2000Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasiasProc. Natl. Acad. Sci. USA9742564261PubMed
22.
go back to reference Narumi, K, Inoue, A, Tanaka, M, et al. 1999Inhibition of experimental metastasis of human fibrosarcoma cells by anti-recombinant 37-kDa laminin binding protein antibodyJpn. J. Cancer Res.90425431PubMed Narumi, K, Inoue, A, Tanaka, M,  et al. 1999Inhibition of experimental metastasis of human fibrosarcoma cells by anti-recombinant 37-kDa laminin binding protein antibodyJpn. J. Cancer Res.90425431PubMed
23.
go back to reference Yazawa, K, Fisher, WE, Brunicardi, FC 2002Current progress in suicide gene therapy for cancerWorld J. Surg.26783789PubMed Yazawa, K, Fisher, WE, Brunicardi, FC 2002Current progress in suicide gene therapy for cancerWorld J. Surg.26783789PubMed
24.
go back to reference Donato, R 2001S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional rolesInt. J. Biochem. Cell. Biol.33637668PubMed Donato, R 2001S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional rolesInt. J. Biochem. Cell. Biol.33637668PubMed
25.
go back to reference Ilg, EC, Schafer, BW, Heizmann, CW 1996Expression pattern of S100 calcium-binding proteins in human tumors, IntJ. Cancer68325332 Ilg, EC, Schafer, BW, Heizmann, CW 1996Expression pattern of S100 calcium-binding proteins in human tumors, IntJ. Cancer68325332
26.
go back to reference Sato, N, Maitra, A, Fukushima, N, et al. 2003Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinomaCancer Res.6341584166PubMed Sato, N, Maitra, A, Fukushima, N,  et al. 2003Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinomaCancer Res.6341584166PubMed
27.
go back to reference Rosty, C, Ueki, T, Argani, P, et al. 2002Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylationAm. J. Pathol.1604550PubMed Rosty, C, Ueki, T, Argani, P,  et al. 2002Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylationAm. J. Pathol.1604550PubMed
28.
go back to reference Chang, K, Pastan, I 1996Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancersProc. Nat. Acad. Sci. USA93136140PubMed Chang, K, Pastan, I 1996Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancersProc. Nat. Acad. Sci. USA93136140PubMed
29.
go back to reference Hassan, R, Viner, JL, Wang, QC, et al. 2000Anti-tumor activity of K1-LysPE38QQR, an immunotoxin targeting mesothelin, a cell-surface antigen overexpressed in ovarian cancer and malignant mesotheliomaJ. Immunother.23473479PubMed Hassan, R, Viner, JL, Wang, QC,  et al. 2000Anti-tumor activity of K1-LysPE38QQR, an immunotoxin targeting mesothelin, a cell-surface antigen overexpressed in ovarian cancer and malignant mesotheliomaJ. Immunother.23473479PubMed
30.
go back to reference Fan, D, Yano, S, Shinohara, H, et al. 2002Targeted therapy against human lung cancer in nude mice by high-affinity recombinant antimesothelin single-chain Fv immunotoxinMol. Cancer Ther.1595600PubMed Fan, D, Yano, S, Shinohara, H,  et al. 2002Targeted therapy against human lung cancer in nude mice by high-affinity recombinant antimesothelin single-chain Fv immunotoxinMol. Cancer Ther.1595600PubMed
31.
go back to reference Argani, P, Iacobuzio-Donahue, C, Ryu, B, et al. 2001Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE)Clin. Cancer Res.738623868PubMed Argani, P, Iacobuzio-Donahue, C, Ryu, B,  et al. 2001Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE)Clin. Cancer Res.738623868PubMed
32.
go back to reference Gu, Z, Thomas, G, Yamashiro, J, et al. 2000Prostate stem cell antigen (PSCA) expression increases with high Gleason score, advanced stage and bone metastasis in prostate cancerOncogene1912881296PubMed Gu, Z, Thomas, G, Yamashiro, J,  et al. 2000Prostate stem cell antigen (PSCA) expression increases with high Gleason score, advanced stage and bone metastasis in prostate cancerOncogene1912881296PubMed
33.
go back to reference Argani, P, Rosty, C, Reiter, RE, et al. 2001Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinomaCancer Res.6143204324PubMed Argani, P, Rosty, C, Reiter, RE,  et al. 2001Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinomaCancer Res.6143204324PubMed
34.
go back to reference Iacobuzio-Donahue, CA, Maitra, A, Olsen, M, et al. 2003Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarraysAm. J. Pathol.16211511162PubMed Iacobuzio-Donahue, CA, Maitra, A, Olsen, M,  et al. 2003Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarraysAm. J. Pathol.16211511162PubMed
35.
go back to reference Samuel, T, Weber, HO, Rauch, P, et al. 2001The G2/M regulator 14-3-3 sigma prevents apoptosis through sequestration of BaxJ. Biol. Chem.2764520145206PubMed Samuel, T, Weber, HO, Rauch, P,  et al. 2001The G2/M regulator 14-3-3 sigma prevents apoptosis through sequestration of BaxJ. Biol. Chem.2764520145206PubMed
36.
go back to reference Sinha, P, Hutter, G, Kottgen, E, et al. 1999Increased expression of epidermal fatty acid binding protein, cofilin, and 14-3-3-sigma (stratifin) detected by two-dimensional gel electrophoresis, mass spectrometry and microsequencing of drug-resistant human adenocarcinoma of the pancreasElectrophoresis.2029522960PubMed Sinha, P, Hutter, G, Kottgen, E,  et al. 1999Increased expression of epidermal fatty acid binding protein, cofilin, and 14-3-3-sigma (stratifin) detected by two-dimensional gel electrophoresis, mass spectrometry and microsequencing of drug-resistant human adenocarcinoma of the pancreasElectrophoresis.2029522960PubMed
37.
go back to reference Ryu, B, Jones, J, Blades, NJ, et al. 2002Relationships and differentially expressed genes among pancreatic cancers examined by large-scale serial analysis of gene expressionCancer Res.62819826PubMed Ryu, B, Jones, J, Blades, NJ,  et al. 2002Relationships and differentially expressed genes among pancreatic cancers examined by large-scale serial analysis of gene expressionCancer Res.62819826PubMed
38.
go back to reference Iacobuzio-Donahue, CA, Ryu, B, Hruban, RH, et al. 2002Exploring the host desmoplastic response to pancreatic carcinoma: gene expression of stromal and neoplastic cells at the site of primary invasionAm J Pathol.1609199PubMed Iacobuzio-Donahue, CA, Ryu, B, Hruban, RH,  et al. 2002Exploring the host desmoplastic response to pancreatic carcinoma: gene expression of stromal and neoplastic cells at the site of primary invasionAm J Pathol.1609199PubMed
39.
go back to reference Iacobuzio-Donahue, CA, Maitra, A, Shen-Ong, GL, et al. 2002Discovery of novel tumor markers of pancreatic cancer using global gene expression technologyAm. J. Pathol.16012391249PubMed Iacobuzio-Donahue, CA, Maitra, A, Shen-Ong, GL,  et al. 2002Discovery of novel tumor markers of pancreatic cancer using global gene expression technologyAm. J. Pathol.16012391249PubMed
Metadata
Title
Gene Overexpression in Pancreatic Adenocarcinoma: Diagnostic and Therapeutic Implications
Authors
Joel A. Rodriguez, B.A.
Min Li, Ph.D.
Qizhi Yao, M.D., Ph.D.
Changyi Chen, M.D., Ph.D.
William E. Fisher, M.D.
Publication date
01-03-2005
Publisher
Springer-Verlag
Published in
World Journal of Surgery / Issue 3/2005
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-004-7843-0

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