title: Clinical significance of increased guanine nucleotide exchange factor Vav3 expression in human gastric cancer.
abstract: Although gastric cancer is one of the most common malignancies worldwide, little is known on the molecular process of its development and progression. This study investigates the involvement of guanine nucleotide exchange factor Vav3 in tumor progression and in the prognosis of human gastric cancer. The two patient cohorts in this study consisted of 167 gastric cancer cases from 1997 through 2001, documenting pathologic and clinical factors, as well as the clinical outcomes. Immunohistochemistry, reverse transcription PCR, immunoblotting, and immunofluorescence were used to examine Vav3 expression in tumor and nontumor pairs of gastric tissues and gastric cell lines. Small hairpin RNA (shRNA) technology was used to study the effects of Vav3 knockdown on the growth and spread of gastric cancer cells. Finally, xenograph proliferation was used to study the tumor growth. Overexpression of Vav3 was associated with the depth of invasion (P = 0.0004), nodal status (P = 0.0260), distant metastasis (P = 0.0003), stage (P = 0.0002), and vascular invasion (P = 0.0286); and correlated with poor disease-free survival (P < 0.0001). Multivariate Cox regression analysis shows that overexpression of Vav3 is an independent prognostic marker for gastric cancer (P = 0.033). Disrupting the expression of Vav3 using shRNA technology inhibited gastric cancer cell growth, spread, and xenograph proliferation. This study suggests that overexpression of Vav3 can be a useful marker for predicting the outcome of patients with gastric cancer and that Vav3 targeting can represent a potential modality for treating gastric cancer.
authors.affiliation: Department of Medical Research, Chi Mei Hospital Chiali, 606, Shin-Hwa Road, Chiali District, Tainan 722, Taiwan.
authors.forename: Kai-Yuan
authors.initials: KY
authors.lastname: Lin
authors.forename: Lu-Hai
authors.initials: LH
authors.lastname: Wang
authors.forename: You-Cheng
authors.initials: YC
authors.lastname: Hseu
authors.forename: Chia-Lang
authors.initials: CL
authors.lastname: Fang
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yang
authors.forename: K J Senthil
authors.initials: KJ
authors.lastname: Kumar
authors.forename: Chein
authors.initials: C
authors.lastname: Tai
authors.forename: Yih-Huei
authors.initials: YH
authors.lastname: Uen
mesh_terms: D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D051567:Proto-Oncogene Proteins c-vav; C496621:VAV3 protein, human