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(American Journal of Pathology. 2000;156:2007-2015.)
© 2000 American Society for Investigative Pathology

Regular Articles

Human Gastric Cancer Kinase Profile and Prognostic Significance of MKK4 Kinase

Chew-Wun Wu^*, Anna F.-Y. Li, Chin-Wen Chi, Chen Lung Huang^*, King-Han Shen^*, Wing-Yiu Liu^* and Wen-chang Lin^§

From the Departments of Surgery,^*
Pathology,
and Medical Research and Education,
Veterans General Hospital–Taipei and School of Medicine, National Yang-Ming University; and the Institute of Biomedical Sciences,^§
Academia Sinica, Taipei, Taiwan, Republic of China

Alterations of protein tyrosine kinase are often associated with uncontrolled cell growth and tumor progression. Knowledge of the overall expression pattern of tyrosine kinases should prove beneficial in understanding the signaling pathways involved in gastric cancer oncogenesis and in providing possible biomarkers for gastric cancer progression. To establish a general tyrosine-kinase expression profile, degenerated polymerase chain reaction primers designed from the consensus catalytic kinase motifs were used to amplify protein tyrosine kinase molecules from gastric cancer tissues. We observed more than 50 tyrosine and serine/threonine kinases from matching pairs of gastric cancer tissue and normal mucosa. Based on this new kinase profile information, we selected the MKK4 gene for further immunohistochemical studies. Statistical analysis of MKK4 protein expression and clinicopathological features indicated that MKK4 kinase expression could serve as a significant prognostic factor for relapse-free survival and for overall survival. We demonstrated a simple and sensitive method for establishing protein tyrosine-kinase expression profiles of human gastric cancer tissues as well as for discovering novel and useful clinical biomarkers from such kinase expression profiles.

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