ABSTRACT
BACKGROUND: China has a high incidence rate and low survival rate of gastric cancer. Therefore, there is a great need to further identify novel oncogenes and clinically applicable molecular targets for the diagnosis and treatment of this disease. METHODS: Expressions of PRRX1, Smad2, epithelial phenotype marker E-cadherin, and interstitial phenotype vimentin protein in a sample of 64 gastric carcinoma and adjacent nontumorous tissues were detected by immunohistochemistry. Their relationship and correlations with clinicopathological features were analyzed. RESULTS: The positive rates of PRRX1, Smad2, E-cadherin, and vimentin protein in primary tumors were 60.94% (39/64), 59.38% (38/64), 34.38%(22/64), and 64.06% (41/64), respectively. A significant correlation was found among the expression of PRRX1, Smad2, E-cadherin, and vimentin (P < 0.05). Expression of the PRRX1, Smad2, and vimentin protein in gastric cancer tissue was correlated with Borrmann classification, lymph node-positive number, the degree of differentiation, depth of tumor invasion, and serum pepsinogen I (PGI) level (P < 0.05), but not with age, sex, serum carcinoembryonic antigen, serum CA199, or PGI/PGII (P > 0.05). CONCLUSION: The positive rate of PRRX1 protein expression was positively correlated with the protein expression of Smad2 and vimentin, but negatively correlated with E-cadherin protein. PRRX1, Smad2, and vimentin proteins are associated with Borrmann type, lymph node positives, histologic grade, depth of tumor invasion, and serum PGI levels, all of which contribute to a poor prognosis for patients with gastric cancer.
Subject(s)
Stomach Neoplasms , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cadherins/genetics , Epithelial-Mesenchymal Transition/genetics , Genes, Homeobox , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Prognosis , Smad2 Protein/genetics , Smad2 Protein/metabolism , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Vimentin/genetics , Vimentin/metabolismABSTRACT
OBJECTIVE: To explore inhibitory effects of S-adenosylmethionine on vascular endothelial growth factor-C (VEGF-C) protein and cellular proliferation in gastric cancer by regulating methylation status of VEGF-C promoter. METHODS: MTT analyses and nude mice model were employed to examine the effects of S- adenosylmethionine on inhibiting gastric cancer growth in vitro and in vivo. The protein expression of VEGF-C in gastric cancer cells was assessed by Western blot. The methylation status of VEGF-C promoter was assessed by bisulfite genomic DNA sequencing analysis. RESULTS: VEGF-C promoter was hypomethylated in MGC803 and SGC7901. The treatment of S-adenosylmethionine resulted in a heavy hypermethylation of VEGF-C promoter, which consequently down regulated protein level of VEGF-C. S-adenosylmethionine effectively inhibited the growth of gastric cancer cells in vitro and in vivo (P<0. 05). CONCLUSION: S-adenosylmethionine can effectively reverse DNA hypomethylation on VEGF-C promoter which down-regulates VEGF-C protein expression and inhibit gastric cancer growth.
