Skip to main content
Top
Published in: World Journal of Surgery 8/2014

01-08-2014

cDNA-Microarray Analysis as a New Tool to Predict Lymph Node Metastasis in Gastric Cancer

Authors: V. Ojetti, R. Persiani, F. C. M. Cananzi, C. Sensi, A. C. Piscaglia, N. Saulnier, A. Biondi, A. Gasbarrini, D. D’Ugo

Published in: World Journal of Surgery | Issue 8/2014

Login to get access

Abstract

Background

The aim of the present study was to investigate whether microarray gene expression analysis can be used to predict lymph node status in gastric cancer.

Methods

Twenty-nine patients undergoing gastrectomy for cancer were enrolled and subdivided according to the pathologic nodal involvement of their disease (N+ vs N0). Molecular profiling was performed by cDNA microarray on tumor tissue and healthy mucosa. Data were processed to identify differently expressed genes. Selected genes were categorized with gene ontology.

Results

Compared to healthy gastric mucosa, 52 genes were differently expressed in N+ patients, and 50 genes in N0 patients. Forty-five genes were similarly regulated in N+ and N0 patients, whereas 12 genes were differently expressed between N+ and N0 patients. Seven genes were exclusively expressed in N+ patients: Egr-1 was upregulated; Claudin-18, AKR1C2, Cathepsin E, CA II, TFF 1, and progastricsin were downregulated. Five genes were exclusively expressed in N0 patients: Complement C5 receptor 1, PLA2/VII, and MMP- 9 were upregulated; MAO-A and ID-4 were downregulated.

Conclusions

Microarray analysis could be a valuable tool to identify genes associated with lymph node metastasis in gastric cancer. This technique could improve the selection of patients with locally advanced disease who are candidates for extended lymph node dissection, multimodal treatment options, or alternative therapeutic strategies.
Literature
1.
2.
go back to reference Macdonald JS, Smalley SR, Benedetti J et al (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725–730PubMedCrossRef Macdonald JS, Smalley SR, Benedetti J et al (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725–730PubMedCrossRef
3.
go back to reference Cunningham D, Allum WH, Stenning SP et al (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–24PubMedCrossRef Cunningham D, Allum WH, Stenning SP et al (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–24PubMedCrossRef
4.
go back to reference Boige V, Pignon J, Saint-Aubert B et al (2007) Final results of a randomized trial comparing preoperative 5-fluorouracil (F)/cisplatin (P) to surgery alone in adenocarcinoma of stomach and lower esophagus (ASLE): FNLCC ACCORD07-FFCD 9703 trial. J Clin Oncol 25:18S Boige V, Pignon J, Saint-Aubert B et al (2007) Final results of a randomized trial comparing preoperative 5-fluorouracil (F)/cisplatin (P) to surgery alone in adenocarcinoma of stomach and lower esophagus (ASLE): FNLCC ACCORD07-FFCD 9703 trial. J Clin Oncol 25:18S
5.
go back to reference Sakuramoto S, Sasako M, Yamaguchi T et al (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820PubMedCrossRef Sakuramoto S, Sasako M, Yamaguchi T et al (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820PubMedCrossRef
6.
go back to reference Yung-Jue B, Young-Woo K, Han-Kwang Y et al (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomized controlled trial. Lancet 379:315–321CrossRef Yung-Jue B, Young-Woo K, Han-Kwang Y et al (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomized controlled trial. Lancet 379:315–321CrossRef
8.
go back to reference Kondo T, Oue N, Yoshida K et al (2004) Expression of POT-1 is associated with tumor stage and telomere length in gastric carcinoma. Cancer Res 64:523–529PubMedCrossRef Kondo T, Oue N, Yoshida K et al (2004) Expression of POT-1 is associated with tumor stage and telomere length in gastric carcinoma. Cancer Res 64:523–529PubMedCrossRef
9.
go back to reference Beer DG, Kardia SL, Huang CC et al (2002) Gene expression profiles predict survival of patients with lung adenocarcinoma. Nat Med 8:816–824PubMed Beer DG, Kardia SL, Huang CC et al (2002) Gene expression profiles predict survival of patients with lung adenocarcinoma. Nat Med 8:816–824PubMed
10.
go back to reference van de Vijver MJ, He YD, van’t Veer LJ (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009PubMedCrossRef van de Vijver MJ, He YD, van’t Veer LJ (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009PubMedCrossRef
11.
go back to reference Croner RS, Peters A, Bruecke WM et al (2005) Microarray versus conventional prediction of lymph node metastasis in colorectal carcinoma. Cancer 104:395–404PubMedCrossRef Croner RS, Peters A, Bruecke WM et al (2005) Microarray versus conventional prediction of lymph node metastasis in colorectal carcinoma. Cancer 104:395–404PubMedCrossRef
12.
go back to reference Hippo Y, Taniguchi H, Tsutsumi S et al (2002) Global gene expression analysis of gastric cancer by oligonucleotide microarrays. Cancer Res 62:233–240PubMed Hippo Y, Taniguchi H, Tsutsumi S et al (2002) Global gene expression analysis of gastric cancer by oligonucleotide microarrays. Cancer Res 62:233–240PubMed
13.
go back to reference El Rifai W, Frierson HF Jr, Harper JC et al (2001) Expression profiling of gastric adenocarcinoma using cDNA array. Int J Cancer 92:832–838PubMedCrossRef El Rifai W, Frierson HF Jr, Harper JC et al (2001) Expression profiling of gastric adenocarcinoma using cDNA array. Int J Cancer 92:832–838PubMedCrossRef
15.
go back to reference Ashburner M, Ball CA, Blake JA, et al (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25–29 Ashburner M, Ball CA, Blake JA, et al (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25–29
16.
go back to reference Kobayashi D, Yamada M, Kamagata C et al (2002) Overexpression of early growth response-1 as a metastasis-regulatory factor in gastric cancer. Anticancer Res 22:3963–3970PubMed Kobayashi D, Yamada M, Kamagata C et al (2002) Overexpression of early growth response-1 as a metastasis-regulatory factor in gastric cancer. Anticancer Res 22:3963–3970PubMed
17.
go back to reference Zheng L, Pu J, Jiang G et al (2010) Abnormal expression of early growth response 1 in gastric cancer: association with tumor invasion, metastasis and heparanase transcription. Pathol Int 60:268–277PubMedCrossRef Zheng L, Pu J, Jiang G et al (2010) Abnormal expression of early growth response 1 in gastric cancer: association with tumor invasion, metastasis and heparanase transcription. Pathol Int 60:268–277PubMedCrossRef
18.
go back to reference Heiskala M, Peterson PA, Yang Y et al (2001) The roles of claudin superfamily proteins in paracellular transport. Traffic 2:93–98PubMedCrossRef Heiskala M, Peterson PA, Yang Y et al (2001) The roles of claudin superfamily proteins in paracellular transport. Traffic 2:93–98PubMedCrossRef
19.
go back to reference Sanada Y, Oue N, Mitani Y et al (2006) Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype. J Pathol 208:633–642PubMedCrossRef Sanada Y, Oue N, Mitani Y et al (2006) Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype. J Pathol 208:633–642PubMedCrossRef
20.
go back to reference Huang KH, Chiou SH, Chow KC et al (2010) Overexpression of aldo-ketoreductase 1C2 is associated with disease progression in patients with prostatic cancer. Histopathology 57:384–394PubMedCrossRef Huang KH, Chiou SH, Chow KC et al (2010) Overexpression of aldo-ketoreductase 1C2 is associated with disease progression in patients with prostatic cancer. Histopathology 57:384–394PubMedCrossRef
21.
go back to reference Tatnell PJ, Cook M, Kay J (2003) An alternatively spliced variant of cathepsin E in human gastric adenocarcinoma cells. Biochim Biophys Acta 1625:203–206PubMedCrossRef Tatnell PJ, Cook M, Kay J (2003) An alternatively spliced variant of cathepsin E in human gastric adenocarcinoma cells. Biochim Biophys Acta 1625:203–206PubMedCrossRef
22.
go back to reference Kivela AJ, Kivela J, Saarnio J et al (2005) Carbonic anhydrases in normal gastrointestinal tract and gastrointestinal tumors. World J Gastroenterol 11:155–163PubMed Kivela AJ, Kivela J, Saarnio J et al (2005) Carbonic anhydrases in normal gastrointestinal tract and gastrointestinal tumors. World J Gastroenterol 11:155–163PubMed
23.
24.
go back to reference Soutto M, Belkhiri A, Piazuelo MB et al (2011) Loss of TFF1 is associated with activation of NF-κB-mediated inflammation and gastric neoplasia in mice and humans. Clin Invest 121:1753–1767CrossRef Soutto M, Belkhiri A, Piazuelo MB et al (2011) Loss of TFF1 is associated with activation of NF-κB-mediated inflammation and gastric neoplasia in mice and humans. Clin Invest 121:1753–1767CrossRef
25.
go back to reference Hassan MI, Toor A, Ahmad F (2010) Progastriscin: structure, function, and its role in tumor progression. J Mol Cell Biol 2:118–127PubMedCrossRef Hassan MI, Toor A, Ahmad F (2010) Progastriscin: structure, function, and its role in tumor progression. J Mol Cell Biol 2:118–127PubMedCrossRef
26.
go back to reference Sun LP, Guo XL, Zhang Y et al (2009) Impact of pepsinogen C polymorphism on individual susceptibility to gastric cancer and its precancerous conditions in a Northeast Chinese population. J Cancer Res Clin Oncol 135:1033–1039PubMedCrossRef Sun LP, Guo XL, Zhang Y et al (2009) Impact of pepsinogen C polymorphism on individual susceptibility to gastric cancer and its precancerous conditions in a Northeast Chinese population. J Cancer Res Clin Oncol 135:1033–1039PubMedCrossRef
27.
go back to reference Melle C, Ernst G, Schimmel B et al (2005) Characterization of pepsinogen C as a potential biomarker for gastric cancer using a histo-proteomic approach. J Proteome Res 4:1799–1804PubMedCrossRef Melle C, Ernst G, Schimmel B et al (2005) Characterization of pepsinogen C as a potential biomarker for gastric cancer using a histo-proteomic approach. J Proteome Res 4:1799–1804PubMedCrossRef
28.
go back to reference Kon OL, Yip TT, Ho MF et al (2008) The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile. BMC Med Genomics 25:1–54 Kon OL, Yip TT, Ho MF et al (2008) The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile. BMC Med Genomics 25:1–54
30.
go back to reference Sanchez LM, Freije JP, Merino AM et al (1992) Isolation and characterization of a pepsin C zymogen produced by human breast tissues. J Biol Chem 267:24725–24731PubMed Sanchez LM, Freije JP, Merino AM et al (1992) Isolation and characterization of a pepsin C zymogen produced by human breast tissues. J Biol Chem 267:24725–24731PubMed
31.
go back to reference Xing XF, Li H, Zhong XY et al (2011) Phospholipase A2 group IIA expression correlates with prolonged survival in gastric cancer. Histopathology 59:198–206PubMed Xing XF, Li H, Zhong XY et al (2011) Phospholipase A2 group IIA expression correlates with prolonged survival in gastric cancer. Histopathology 59:198–206PubMed
32.
go back to reference Jolly K, Cheng KK, Langman MJ et al (2002) NSAIDs and gastrointestinal cancer prevention. Drugs 62:945–956PubMedCrossRef Jolly K, Cheng KK, Langman MJ et al (2002) NSAIDs and gastrointestinal cancer prevention. Drugs 62:945–956PubMedCrossRef
33.
go back to reference Yang S, Zhao Z, Wu R et al (2011) Expression and biological relationship of vascular endothelial growth factor-A and matrix metalloproteinase-9 in gastric carcinoma. J Int Med Res 39:2076–2085PubMedCrossRef Yang S, Zhao Z, Wu R et al (2011) Expression and biological relationship of vascular endothelial growth factor-A and matrix metalloproteinase-9 in gastric carcinoma. J Int Med Res 39:2076–2085PubMedCrossRef
34.
go back to reference Chu D, Zhang Z, Li Y et al (2011) Matrix metalloproteinase-9 is associated with disease-free survival and overall survival in patients with gastric cancer. Int J Cancer 129:887–895PubMedCrossRef Chu D, Zhang Z, Li Y et al (2011) Matrix metalloproteinase-9 is associated with disease-free survival and overall survival in patients with gastric cancer. Int J Cancer 129:887–895PubMedCrossRef
35.
go back to reference Yang Q, Ye ZY, Zhang JX et al (2010) Expression of matrix metalloproteinase-9 mRNA and vascular endothelial growth factor protein in gastric carcinoma and its relationship to its pathological features an prognosis. Anat Rec (Hoboken) 293:2012–2019CrossRef Yang Q, Ye ZY, Zhang JX et al (2010) Expression of matrix metalloproteinase-9 mRNA and vascular endothelial growth factor protein in gastric carcinoma and its relationship to its pathological features an prognosis. Anat Rec (Hoboken) 293:2012–2019CrossRef
36.
go back to reference Mroczko B, Lukaszewicz-Zajac M, Guzinska-Ustymowicz K et al (2009) Expression of matrix metalloproteinase-9 in the neoplastic and interstitial inflammatory infiltrate cells in gastric cancer. Folia Histochem Cytobiol 47:491–496PubMed Mroczko B, Lukaszewicz-Zajac M, Guzinska-Ustymowicz K et al (2009) Expression of matrix metalloproteinase-9 in the neoplastic and interstitial inflammatory infiltrate cells in gastric cancer. Folia Histochem Cytobiol 47:491–496PubMed
37.
go back to reference Sun WH, Sun YL, Fang RN et al (2005) Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis. Jpn J Clin Oncol 35:707–713PubMedCrossRef Sun WH, Sun YL, Fang RN et al (2005) Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis. Jpn J Clin Oncol 35:707–713PubMedCrossRef
38.
go back to reference Tang Y, Zhu J, Chen L et al (2008) Associations of matrix metalloproteinase-9 protein polymorphisms with lymph node metastasis but not invasion of gastric cancer. Clin Cancer Res 14:2780–2787 Tang Y, Zhu J, Chen L et al (2008) Associations of matrix metalloproteinase-9 protein polymorphisms with lymph node metastasis but not invasion of gastric cancer. Clin Cancer Res 14:2780–2787
39.
go back to reference Rybaczyk LA, Bashaw MJ, Pathak DR et al (2008) An indicator of cancer: downregulation of monoamine oxidase-A in multiple organs and species. BMC Genomics 9:134PubMedCentralPubMedCrossRef Rybaczyk LA, Bashaw MJ, Pathak DR et al (2008) An indicator of cancer: downregulation of monoamine oxidase-A in multiple organs and species. BMC Genomics 9:134PubMedCentralPubMedCrossRef
Metadata
Title
cDNA-Microarray Analysis as a New Tool to Predict Lymph Node Metastasis in Gastric Cancer
Authors
V. Ojetti
R. Persiani
F. C. M. Cananzi
C. Sensi
A. C. Piscaglia
N. Saulnier
A. Biondi
A. Gasbarrini
D. D’Ugo
Publication date
01-08-2014
Publisher
Springer US
Published in
World Journal of Surgery / Issue 8/2014
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-014-2529-8

Other articles of this Issue 8/2014

World Journal of Surgery 8/2014 Go to the issue