Downregulation of ABI1 expression affects the progression and prognosis of human gastric carcinoma

Abstract

Abelson interactor protein-1 (ABI1) is a promising candidate tumor suppressor, and plays critical roles both in the pathogenesis of BCR-Abl-induced leukemia and in the spread of several solid tumors. The expression of ABI1 and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors, including gastric cancer. In this study, we analyzed the correlation between ABI1 expression and the clinicopathological characteristics, tumor progression, and prognosis of patients with gastric carcinoma. Tissue specimens were from 103 gastric cancer patients who underwent gastrectomy in our hospital between January 2000 and December 2007. Among them 59 tumor tissue samples were matched with normal tissue samples. The expression of ABI1 protein was measured using immunohistochemical staining of paraffin-embedded tissue specimens. Meanwhile, quantitative real-time RT-PCR and Western blotting were used to identify the expression of ABI1 in human gastric normal mucosal cell line (GES-1) and gastric cancer cell lines (N87, AGS). We performed a statistical analysis of the potential correlation between ABI1 expression and the patients' clinicopathological characteristics, 5-year survival, and median survival time. The immunohistochemical staining results of 59 patients showed that ABI1 was expressed in 28.8% (17/59) of gastric cancer tissues, compared to 91.5% (54/59) of normal samples. ABI1 expression in 103 patients was strongly correlated with tumor differentiation, clinical stage, and lymph node status (P < 0.01). The 5-year survival rate was 15.3% in the ABI1-negative group and 63.7% in the ABI1-positive group. Median survival time in the ABI1-negative and ABI1-positive groups was 25.0 months (95% CI: 19.7-30.3) and 74.0 months (95% CI: 54.6-93.3), respectively. There was a significant difference between the two groups (chi(2) = 10.888, P = 0.001). Furthermore, we found that ABI1 expressed lowly in poor differentiated AGS, whereas highly in GES-1 and well-differentiated N87. Downregulation of ABI1 expression in human gastric carcinoma may play a critical role in tumor progression and in determining patient prognosis. ABI1 may be a useful diagnostic or prognostic molecular biomarker, and might be a potential target for therapeutic intervention.