Microarray analysis identifies versican and CD9 as potent prognostic markers in gastric gastrointestinal stromal tumors.
Although the main cause of gastrointestinal stromal tumor (GIST) is gain-of-function mutations in the c-kit gene in the interstitial cells of Cajal, concomitant genetic or epigenetic changes other than c-kit appear to occur in the development of metastasis. We sought to identify the genes involved in the metastatic process of gastric GIST. Microarray analysis was performed to compare gene expressions between three gastric GIST and four metastatic liver GIST. Expression levels were higher for 165 genes and lower for 146 genes in metastatic liver GIST. The upregulation of five oncogenes and downregulation of four tumor suppressor genes including versican and CD9 were confirmed by quantitative reverse transcriptional PCR. Immunohistochemistry in 117 GIST revealed that protein levels of versican and CD9 were higher and lower, respectively, in metastatic GIST. High expression of versican and low expression of CD9 in 104 primary gastric GIST correlated with poor disease-free survival (P = 0.0078 and P = 0.0018). In addition to the c-kit gene mutation, genetic or epigenetic changes other than c-kit play important roles in the metastatic process. In particular, versican and CD9 are potential prognostic markers in gastric GIST.
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Tomohiko
T
Setoguchi
Hirotoshi
H
Kikuchi
Masayoshi
M
Yamamoto
Megumi
M
Baba
Manabu
M
Ohta
Kinji
K
Kamiya
Tatsuo
T
Tanaka
Satoshi
S
Baba
Naoko
N
Goto-Inoue
Mitsutoshi
M
Setou
Takeshi
T
Sasaki
Hiroki
H
Mori
Haruhiko
H
Sugimura
Hiroyuki
H
Konno
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D060245:Tetraspanin 29; D053675:Versicans / Q000235:genetics* / Q000378:metabolism
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D060245:Tetraspanin 29; D053675:Versicans; D019009:Proto-Oncogene Proteins c-kit
Cancer Res. 1999 Sep 1;59(17):4297-300
10485475
J Pathol. 2007 Mar;211(4):463-70
17226762
Genes Chromosomes Cancer. 2007 Mar;46(3):261-76
17171690
Nature. 2009 Jan 1;457(7225):102-6
19122641
Cancer Sci. 2006 Feb;97(2):127-32
16441423
Cancer Res. 2005 Jan 15;65(2):448-56
15695386
Cancer. 2008 Oct 1;113(7):1532-43
18671247
Clin Cancer Res. 2004 Nov 1;10(21):7304-10
15534106
Cancer Metastasis Rev. 2009 Jun;28(1-2):233-45
19160015
Exp Cell Res. 2007 Mar 10;313(5):1033-44
17275810
J Biomed Sci. 2004 Jan-Feb;11(1):65-71
14730211
Science. 1998 Jan 23;279(5350):577-80
9438854
Hum Pathol. 2006 Dec;37(12):1527-35
16996566
Hum Pathol. 2002 May;33(5):478-83
12094372
Am J Surg Pathol. 2007 Jan;31(1):113-20
17197927
Cancer Res. 2009 Feb 1;69(3):879-86
19176371
Cancer Metastasis Rev. 2006 Sep;25(3):387-408
17043764
Cancer Res. 2004 Sep 1;64(17):5913-9
15342366
Jpn J Cancer Res. 2000 Dec;91(12):1241-9
11123422
Nat Rev Cancer. 2009 Jan;9(1):40-55
19078974
Cancer Res. 2001 Nov 15;61(22):8118-21
11719439
Clin Cancer Res. 2008 Mar 15;14(6):1707-17
18347171
Semin Diagn Pathol. 2006 May;23(2):70-83
17193820
Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a003129
20457567
Am J Pathol. 2000 Mar;156(3):791-5
10702394
Science. 2003 Jan 31;299(5607):708-10
12522257
J Pathol. 2001 Apr;193(4):505-10
11276010
Gastroenterology. 2005 Feb;128(2):270-9
15685537
Cancer Res. 2000 Jul 15;60(14):3899-903
10919666
Hum Pathol. 2001 Apr;32(4):396-400
11331956
Cancer Res. 2010 May 1;70(9):3823-32
20388805
J Mol Biol. 2000 Jun 9;299(3):551-72
10835267
Cancer Sci. 2007 Nov;98(11):1734-9
17894554
Int J Surg Pathol. 2002 Apr;10(2):81-9
12075401
Clin Cancer Res. 2003 Aug 15;9(9):3329-37
12960119
J Formos Med Assoc. 2009 Jan;108(1):28-37
19181605
Genes Chromosomes Cancer. 2007 Jun;46(6):564-76
17330260
Ann Surg. 2000 Jan;231(1):51-8
10636102
Clin Cancer Res. 2006 Sep 1;12(17):5136-41
16951231
Mod Pathol. 2004 Nov;17(11):1364-71
15181453
Gastroenterology. 2009 Feb;136(2):640-51.e1
19084528
Eur J Cancer. 2002 Sep;38 Suppl 5:S37-8
12528771
Oncol Rep. 2006 Oct;16(4):915-9
16969514
Lancet. 2009 Mar 28;373(9669):1097-104
19303137
Clin Cancer Res. 2005 Jun 1;11(11):4182-90
15930355
Gastroenterology. 2004 Jul;127(1):294-9
15236194
Gastroenterology. 2003 Sep;125(3):660-7
12949711
J Clin Oncol. 2008 Sep 1;26(25):4100-8
18757323
N Engl J Med. 2001 Apr 5;344(14):1052-6
11287975
Genes Chromosomes Cancer. 2009 Nov;48(11):983-92
19681120
Lancet. 2001 Oct 27;358(9291):1421-3
11705489
J Pharmacol Exp Ther. 2000 Oct;295(1):139-45
10991971