Back to Annual Meeting Program

BACKGROUND: Gastric cancer is the second most common cancer worldwide and the sixth leading cause of cancer-related death in Taiwan. Biomarkers are investigated to improve early detection and patient survival. Previously, ARF1 was identified as one of the strongest upregulated proteins by using proteomic technique: two-dimensional (2D) gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ARF1 belongs to the Ras superfamily or GTP-binding protein family and has been shown to enhance cell proliferation.
SUBJECTS & METHODS: A total of 110 patients (69 males, 41 females; median age: 66 years, range 28-86 years) with gastric cancer undergoing gastrectomy were enrolled into this study. Real-time quantitative RT-PCR, western blot analysis and immunohistochemistry (IHC) on resected specimens were used to confirm the ARF1 overexpression in surgical patients. The clinical significance of ARF1 expression was evaluated by clinicopathological correlations and patient’s suruvial outcome. To establish the specific function of ARF1 in human gastric cancer, isogenic ARF1-overexpressing cell lines were prepared.
RESULTS: Expression of ARF1 mRNA was significantly upregulated in 67.2% of gastric cancer patients by using Real-time quantitative RT-PCR test. Paired comparison of IHC study for ARF1 revealed that the IHC scores of cancerous tissues were higher than those of the nontumorous counterparts in 76.5% of patients. Elevated ARF1 expression was strongly correlated with lymph node metastasis (p = 0.008), serosal invasion (p =0.046), lymphatic invasion (p = 0.035) and pathological staging (p = 0.010). Moreover, the 5-year survival rate for the lower ARF1 expression group (n = 50; IHC score <90) was higher than that of the higher expression group (n = 60; IHC score ≥90) (log rank p = 0.0228). Our functional studies also demonstrate that ARF1-overexpressing clones display enhanced cell proliferation, migration and invasion.
DISCUSSION & CONCLUSION: ARF, a family of small GTP-binding proteins, play important roles in intracellular trafficking in animal and yeast cells. Over-expression of ARF1 in cancer cells has been reported in human breast cancer cells. ARF1 regulates breast cancer cell growth and invasion during cancer progression. Our data demonstrated that expression of ARF1 is associated with tumor progression and survival outcome. And, it might be a potential prognostic marker for gastric cancer. These findings collectively support the utility of ARF1 as a potential prognostic marker for gastric cancer and its role in cell invasion.