Gene expression profiling of metaplastic lineages identifies CDH17 as a prognostic marker in early stage gastric cancer.
OBJECTIVE
Intestinal metaplasia (IM) and spasmolytic polypeptide-expressing metaplasia (SPEM) are precursors to gastric carcinogenesis. We sought to identify molecular biomarkers of gastric metaplasias and gastric cancer by gene expression profiling of metaplastic lesions from patients.


METHODS
Complementary DNA microarray analysis was performed on IM and SPEM cells isolated from patient samples using laser capture microdissection. Up-regulated transcripts in metaplastic lesions were confirmed by immunostaining analysis in IM, SPEM, and gastric cancer tissues. Proteins that were highly expressed specifically in gastric cancer tissues were analyzed for their association with survival in a test set (n = 450) and a validation set (n = 502) of samples from gastric cancer patients.


RESULTS
Compared with normal chief cells, 858 genes were differentially expressed in IM or SPEM samples. Immunostaining was detected for 12 proteins, including 3 new markers of IM (ACE2, LGALS4, AKR1B10) and 3 of SPEM (OLFM4, LYZ, DPCR1). Of 13 proteins expressed in IM or SPEM, 8 were expressed by 17%-50% of human gastric cancer tissues (MUC13, OLFM4, CDH17, KRT20, MUC5AC, LGALS4, AKR1B10, REG4). Expression of CDH17 or MUC13 correlated with patient survival in the test and validation sets. Multivariate analysis showed that CDH17 was an independent prognostic factor in patients with stage I or node-negative disease.


CONCLUSIONS
We identified several novel biomarkers for IM, SPEM, and gastric cancer using gene expression profiling of human metaplastic lesions. Expression of CDH17 and MUC13 was up-regulated in gastric cancer tissues. CDH17 is a promising prognostic marker for early stage gastric cancer.
Lee
Hyuk-Joon
HJ
Department of Surgery, Vanderbilt University College of Medicine, Epithelial Biology Center, Nashville, Tennessee 37232-2733, USA.
Nam
Ki Taek
KT
Park
Heae Surng
HS
Kim
Min A
MA
Lafleur
Bonnie J
BJ
Aburatani
Hiroyuki
H
Yang
Han-Kwang
HK
Kim
Woo Ho
WH
Goldenring
James R
JR
D000368:Aged; D014408:Biomarkers, Tumor; D015820:Cadherins / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D020869:Gene Expression Profiling; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D009077:Mucins / Q000235:genetics; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010455:Peptides / Q000235:genetics; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*
D014408:Biomarkers, Tumor; C490584:CDH17 protein, human; D015820:Cadherins; D036341:Intercellular Signaling Peptides and Proteins; C429552:MUC13 protein, human; D009077:Mucins; C454127:OLFM4 protein, human; D010455:Peptides; C451060:spasmolytic polypeptide; D016179:Granulocyte Colony-Stimulating Factor
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