Clinical significance of increased guanine nucleotide exchange factor Vav3 expression in human gastric cancer

Kai Yuan Lin, Lu Hai Wang, You Cheng Hseu, Chia Lang Fang, Hsin Ling Yang, K. J Senthil Kumar, Chein Tai, Yih Huei Uen

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)750-759
Number of pages10
JournalMolecular Cancer Research
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Guanine Nucleotide Exchange Factors
Stomach Neoplasms
Small Interfering RNA
Neoplasms
Stomach
Growth
Technology
Immunoblotting
Reverse Transcription
Disease-Free Survival
Fluorescent Antibody Technique
Blood Vessels
Cohort Studies
Immunohistochemistry
Regression Analysis
Neoplasm Metastasis
Cell Line
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Clinical significance of increased guanine nucleotide exchange factor Vav3 expression in human gastric cancer. / Lin, Kai Yuan; Wang, Lu Hai; Hseu, You Cheng; Fang, Chia Lang; Yang, Hsin Ling; Kumar, K. J Senthil; Tai, Chein; Uen, Yih Huei.

In: Molecular Cancer Research, Vol. 10, No. 6, 06.2012, p. 750-759.

Research output: Contribution to journalArticle

Lin, Kai Yuan ; Wang, Lu Hai ; Hseu, You Cheng ; Fang, Chia Lang ; Yang, Hsin Ling ; Kumar, K. J Senthil ; Tai, Chein ; Uen, Yih Huei. / Clinical significance of increased guanine nucleotide exchange factor Vav3 expression in human gastric cancer. In: Molecular Cancer Research. 2012 ; Vol. 10, No. 6. pp. 750-759.
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