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The Combined Expression of Metaplasia Biomarkers Predicts the Prognosis Of Gastric Cancer

 Yun-Suhk Suh  ;  Hyuk-Joon Lee  ;  Eun-Jung Jung  ;  Min-A Kim  ;  Ki Taek Nam  ;  James R. Goldenring  ;  Han-Kwang Yang  ;  Woo Ho Kim 
 ANNALS OF SURGICAL ONCOLOGY, Vol.19(4) : 1240-1249, 2012 
Journal Title
Issue Date
Adenocarcinoma/chemistry* ; Adenocarcinoma/pathology* ; Biomarkers, Tumor/analysis* ; Cadherins/analysis ; Female ; Galectin 4/analysis ; Gene Expression Profiling ; Granulocyte Colony-Stimulating Factor/analysis ; Humans ; Immunohistochemistry ; Keratin-20/analysis ; Lectins, C-Type/analysis ; Male ; Metaplasia ; Middle Aged ; Mucin 5AC/analysis ; Mucins/analysis ; Neoplasm Staging ; Pancreatitis-Associated Proteins ; Prognosis ; Stomach Neoplasms/chemistry* ; Stomach Neoplasms/pathology*
Gastric Cancer ; Intestinal Metaplasia ; Gastric Cancer Tissue ; Retrieve Lymph Node ; Combine Expression
BACKGROUND: Our previous study indicated that gene expression profiling of intestinal metaplasia (IM) or spasmolytic polypeptide-expressing metaplasia (SPEM) can identify useful prognostic markers of early-stage gastric cancer, and seven metaplasia biomarkers (MUC13, CDH17, OLFM4, KRT20, LGALS4, MUC5AC, and REG4) were selectively expressed in 17-50% of gastric cancer tissues. We investigated whether the combined expression of these metaplasia biomarkers could predict the prognosis of advanced stage gastric cancer. METHODS: The expression of seven metaplasia biomarkers was evaluated immunohistochemically using tissue microarrays comprised of 450 gastric cancer patients. The clinicopathologic correlations and the prognostic impact were analyzed according to the expression of multiple biomarkers. RESULTS: MUC13, CDH17, LGALS4, and REG4 were significant prognostic biomarkers in univariate analysis. No expression of four markers was found in 56 cases (14.2%); 1 marker was seen in 67 cases (17%), 2 in 106 cases (27%), 3 in 101 cases (25.7%), and 4 in 63 cases (16%). Patients in which two or fewer proteins were expressed (group B) showed younger age, undifferentiated or diffuse type cancer, larger tumor size, larger number of metastatic lymph nodes, and more advanced stage than those in which three or more proteins were expressed (group A). In undifferentiated or stage II/III gastric cancer, the prognosis of group B was significantly poorer than that of group A by multivariate analysis. CONCLUSIONS: The combined loss of expression of multiple metaplasia biomarkers is considered an independent prognostic indicator in undifferentiated or stage II/III gastric cancer.
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Yonsei Authors
Nam, Ki Taek(남기택)
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