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tie-1 Protein Tyrosine Kinase: A Novel Independent Prognostic Marker for Gastric Cancer¹

Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China [W-c. L.]; Departments of Pathology [A. F-Y. L., W-W. C.], Medical Research and Education [C-W. C.], and Surgery [C. L. H., W-Y. L., C-W. W.], Veterans General Hospital-Taipei and School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, Republic of China; and Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 [H-J. K.]

Protein tyrosine kinases (PTKs) are a major class of proto-oncogenes that are involved in tumor progression. The purpose of this study was to establish a comprehensive PTK expression profile in gastric cancers, with the objective of identifying possible biomarkers for gastric cancer progression. We have designed degenerate primers according to the consensus catalytic motifs to amplify PTK molecules from gastric cancers by reverse transcriptase-PCR methods. The PTK expression profile was established by sequencing analysis of the cloned PCR products. We have identified 17 PTKs from a gastric adenocarcinoma. Two receptor PTKs, tie-1 and axl, were selected for in situ immunohistochemistry studies because of their higher expression level and their described roles in adhesion, invasion, and angiogenesis. Among the 97 gastric adenocarcinoma tissues examined, we observed positive immunohistochemical staining of tie-1 PTK in 69 and positive staining of axl kinase in 71 tissues. Statistical analysis with clinicopathological features indicates that tie-1 kinase expression is inversely correlated with patients’ survival, whereas axl fails to show similar clinical significance. Our results illustrate the utility of tyrosine kinase gene family profiling in human gastric cancers and show that tie-1 tyrosine kinase may serve as a novel independent prognostic marker for gastric adenocarcinoma patients.

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