The clinical value of Vav3 in peripheral blood for predicting lymphatic metastasis of gastric cancer

Abstract Background: Overexpression of Vav3, a gene involved in signal transduction, promotes invasion and inhibits apoptosis in several cancers. The clinical value of the protein product of this gene, Vav3, in the peripheral blood of gastric cancer patients is unknown. We hypothesised increased serum Vav3 that related to tissue levels and lymph node metastases. In addition, we further explored its clinical value in respect of linked molecules Rac-1, MMP-7 and ICAM-1 Methods: 120 gastric cancer patients who had radical surgery were enrolled. Immunohistochemistry was used to determine the expressions of Vav3, Rac-1, MMP-7 and ICAM-1 in gastric cancer mucosa and normal mucosa. ELISA was used to detect these proteins in peripheral blood of gastric cancer patients and 100 age- and sex-matched healthy controls. Results: Vav3, Rac-1 and MMP-7 (P < 0.001), but not ICAM-1 (P = 0.303) were more highly expressed by cancer tissues than normal gastric mucosa. Serum levels of all molecules were higher than those in healthy subjects (P < 0.001). Levels of Vav3, Rac-1 and MMP-7 decreased 2 weeks postoperatively (all P < 0.001) but there was no change in ICAM-1 (P = 0.192). Similarly, increased levels of Vav3, Rac-1 and MMP-7 were present in patients with lymphatic metastasis than those without (all P < 0.001) but there was no difference in ICAM-1 levels (P = 0.378). There were positive correlations between Vav3 with Rac-1 and MMP-7 in cancer tissues (P < 0.001), and also between Vav3 and Rac-1 in pre-surgery blood (P = 0.003). Conclusions: Vav3 in peripheral blood may serve as a biomarker for gastric cancer, and to predict the lymphatic metastasis in gastric cancer.

[1]  Byung-In Moon,et al.  Syndecan-2 enhances E-cadherin shedding and fibroblast-like morphological changes by inducing MMP-7 expression in colon cancer cells. , 2016, Biochemical and biophysical research communications.

[2]  J. Friedrichs,et al.  Breast cancer cells compete with hematopoietic stem and progenitor cells for intercellular adhesion molecule 1-mediated binding to the bone marrow microenvironment. , 2016, Carcinogenesis.

[3]  Liang Wu,et al.  Overexpression of miR-499-5p inhibits non-small cell lung cancer proliferation and metastasis by targeting VAV3 , 2016, Scientific Reports.

[4]  Kecheng Zhang,et al.  Intercellular adhesion molecule 1 is a sensitive and diagnostically useful immunohistochemical marker of papillary thyroid cancer (PTC) and of PTC-like nuclear alterations in Hashimoto's thyroiditis , 2016, Oncology letters.

[5]  L. Zhu,et al.  A novel KLF6-Rho GTPase axis regulates hepatocellular carcinoma cell migration and dissemination , 2016, Oncogene.

[6]  Yong Li,et al.  Inhibition of Vav3 gene can promote apoptosis of human gastric cancer cell line MGC803 by regulating ERK pathway , 2016, Tumor Biology.

[7]  Ying Sun,et al.  Roles of osteopontin and matrix metalloproteinase-7 in occurrence, progression, and prognosis of nonsmall cell lung cancer , 2015, Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences.

[8]  X. Lang,et al.  Correlation Between MMP-7 and bFGF Expressions in Non-small Cell Lung Cancer Tissue and Clinicopathologic Features , 2015, Cell Biochemistry and Biophysics.

[9]  D. Wang,et al.  Inhibition of Vav3 could reverse the drug resistance of gastric cancer cells by downregulating JNK signaling pathway , 2014, Cancer Gene Therapy.

[10]  Yong Li,et al.  Regulatory mechanism of ZNF139 in multi-drug resistance of gastric cancer cells , 2014, Molecular Biology Reports.

[11]  K. Matsuura,et al.  The Vav3 oncogene enhances the malignant potential of prostate cancer cells under chronic hypoxia. , 2014, Urologic oncology.

[12]  F. Climent,et al.  VAV3 mediates resistance to breast cancer endocrine therapy , 2014, Breast Cancer Research.

[13]  Yong Li,et al.  Inhibition of gastric cancer cell growth and invasion through siRNA-mediated knockdown of guanine nucleotide exchange factor Vav3 , 2014, Tumor Biology.

[14]  X. Bustelo,et al.  Chronic sympathoexcitation through loss of Vav3, a Rac1 activator, results in divergent effects on metabolic syndrome and obesity depending on diet. , 2013, Cell metabolism.

[15]  Yong Li,et al.  Analysis of lymph node dissection range-related factors for early gastric cancer operation. , 2013, Hepato-gastroenterology.

[16]  R. Mejía.  Vav Proteins' Role in Skin Cancer , 2013, PLoS biology.

[17]  K. Matsuura,et al.  Targeting the Vav3 oncogene enhances docetaxel-induced apoptosis through the inhibition of androgen receptor phosphorylation in LNCaP prostate cancer cells under chronic hypoxia , 2013, Molecular Cancer.

[18]  J. Gong,et al.  Expression and role of icam-1 in the occurrence and development of hepatocellular carcinoma. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[19]  K. Burnstein,et al.  Vav3 enhances androgen receptor splice variant activity and is critical for castration-resistant prostate cancer growth and survival. , 2012, Molecular endocrinology.

[20]  Yong Li,et al.  Heterogeneity of COX-2 and multidrug resistance between primary tumors and regional lymph node metastases of gastric cancer. , 2012, Tumori.

[21]  Chien-Feng Li,et al.  Vav3-rac1 signaling regulates prostate cancer metastasis with elevated Vav3 expression correlating with prostate cancer progression and posttreatment recurrence. , 2012, Cancer research.

[22]  P. Gaulard,et al.  Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets. , 2012, Blood.

[23]  M. Shyu,et al.  Zinc oxide nanoparticles-induced intercellular adhesion molecule 1 expression requires Rac1/Cdc42, mixed lineage kinase 3, and c-Jun N-terminal kinase activation in endothelial cells. , 2012, Toxicological sciences : an official journal of the Society of Toxicology.

[24]  J. A. Varela,et al.  Essential Role for Vav Guanine Nucleotide Exchange Factors in Brain-Derived Neurotrophic Factor-Induced Dendritic Spine Growth and Synapse Plasticity , 2011, The Journal of Neuroscience.

[25]  P. Fernández-Salguero.  A remarkable new target gene for the dioxin receptor , 2010, Cell adhesion & migration.

[26]  Z. Dong,et al.  The molecular mechanism of Vav3 oncogene on upregulation of androgen receptor activity in prostate cancer cells. , 2010, International journal of oncology.

[27]  G. Capellá,et al.  Filamin B Plays a Key Role in Vascular Endothelial Growth Factor-induced Endothelial Cell Motility through Its Interaction with Rac-1 and Vav-2* , 2010, The Journal of Biological Chemistry.

[28]  Zhongyun Dong,et al.  Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer , 2008, BMC Cancer.

[29]  C. Rudd,et al.  CTL-Associated Antigen-4 Ligation Induces Rapid T Cell Polarization That Depends on Phosphatidylinositol 3-Kinase, Vav-1, Cdc42, and Myosin Light Chain Kinase1 , 2007, The Journal of Immunology.