title: Downregulation of ZIP kinase is associated with tumor invasion, metastasis and poor prognosis in gastric cancer.
abstract: Deletion of 19p13 is one of the most frequent genetic changes in gastric carcinoma (GC), implying the existence of a tumor suppressor gene (TSG) that plays an important role in GC development. To identify the candidate TSG at 19p, array-comparative genomic hybridization (CGH) was applied to study DNA copy-number changes on chromosomes 3, 5p, 13, 16q and 19. The result showed that gains of 16q21, 19q13.1, 5p15.1 and 3q26.31, and losses of 3p21.32, 3p22.2, 19q13.33 and 19p13.3, were frequently detected by array-CGH. One candidate TSG, ZIP kinase (ZIPK), at 19p13.3 was further characterized by immunohistochemistry using a tissue microarray containing 172 primary GCs. Downregulation of ZIPK was detected in 111/162 informative GCs, which was significantly associated with invasion, metastasis and poorer prognosis of GC. To investigate the association of the downregulation of ZIPK with apoptosis, apoptosis assay (TUNEL) was used to compare the apoptotic index between GCs with normal expression and downregulation of ZIPK. TUNEL assay showed that the apoptotic index in GCs with normal ZIPK expression was significantly higher than that in GCs with downregulation of ZIPK (p < 0.001), indicating that ZIPK plays an important pro-apoptotic role in GC. Taken together, we demonstrated here that ZIPK is a tumor suppresser gene and plays an important role in GC development through its pro-apoptotic function. Downregulation of ZIPK can be used to evaluate tumor invasiveness, metastasis and to predict survival of GC.
authors.affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Bi
authors.forename: Sze-Hang
authors.initials: SH
authors.lastname: Lau
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.forename: Hui-Lan
authors.initials: HL
authors.lastname: Rao
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Liu
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Zhan
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Wen
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D055028:Comparative Genomic Hybridization; D064550:Death-Associated Protein Kinases; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases