ABI1 表达下调影响人胃癌的进展和预后。

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

机构信息

Department of Gastroenterology, People's Hospital, Peking University, 100044, Beijing, People's Republic of China.

出版信息

Med Oncol. 2010 Sep;27(3):632-9. doi: 10.1007/s12032-009-9260-6. Epub 2009 Jun 25.

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.

摘要

Abelson 相互作用蛋白 1(ABI1)是一种有前途的候选肿瘤抑制因子,在 BCR-Abl 诱导的白血病发病机制和几种实体瘤的扩散中都起着关键作用。ABI1 的表达及其在癌症进展和预后中的作用在大多数实体瘤中,包括胃癌中,在很大程度上尚不清楚。在这项研究中,我们分析了 ABI1 表达与胃癌患者的临床病理特征、肿瘤进展和预后之间的相关性。组织标本来自 2000 年 1 月至 2007 年 12 月期间在我院接受胃切除术的 103 例胃癌患者。其中 59 例肿瘤组织标本与正常组织标本相匹配。使用石蜡包埋组织标本的免疫组织化学染色来测量 ABI1 蛋白的表达。同时,使用定量实时 RT-PCR 和 Western blot 鉴定人胃正常黏膜细胞系(GES-1)和胃癌细胞系(N87、AGS)中 ABI1 的表达。我们对 ABI1 表达与患者临床病理特征、5 年生存率和中位生存时间之间的潜在相关性进行了统计学分析。对 59 例患者的免疫组化染色结果显示,28.8%(17/59)的胃癌组织中表达 ABI1,而正常样本中 91.5%(54/59)表达 ABI1。ABI1 在 103 例患者中的表达与肿瘤分化程度、临床分期和淋巴结状态密切相关(P<0.01)。ABI1 阴性组的 5 年生存率为 15.3%,ABI1 阳性组为 63.7%。ABI1 阴性组和 ABI1 阳性组的中位生存时间分别为 25.0 个月(95%CI:19.7-30.3)和 74.0 个月(95%CI:54.6-93.3),两组间差异有统计学意义(chi(2) = 10.888,P = 0.001)。此外,我们发现 ABI1 在低分化 AGS 中表达较低,而在 GES-1 和高分化 N87 中表达较高。人类胃癌中 ABI1 表达下调可能在肿瘤进展和确定患者预后中起关键作用。ABI1 可能是一种有用的诊断或预后分子生物标志物,也可能是治疗干预的潜在靶点。

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