Human gastric cancer kinase profile and prognostic significance of MKK4 kinase

Alterations of protein tyrosine kinase are often associated with uncontroll ed cell growth and tumor progression. Knowledge of the overall expression p attern of tyrosine kinases should prove beneficial in understanding the sig naling pathways involved in gastric cancer oncogenesis and in providing pos sible biomarkers for gastric cancer progression. To establish a general tyr osine-kinase expression profile, degenerated polymerase chain reaction prim ers designed from the consensus catalytic kinase motifs were used to amplif y protein tyrosine kinase molecules from gastric cancer tissues. We observe d 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 stud ies. Statistical analysis of MKK4 protein expression and clinicopathologica l features indicated that MKK4 kinase expression could serve as a significa nt prognostic factor for relapse-free survival and for overall survival. We demonstrated a simple and sensitive method for establishing protein tyrosi ne-kinase expression profiles of human gastric cancer tissues as well as fo r discovering novel and useful clinical biomarkers from such kinase express ion profiles.