Prognostic relevance of Tensin4 expression in human gastric cancer

Prognostic relevance of Tensin4 expression in human gastric cancer
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DOI:
10.1245/s10434-008-9989-8
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发表时间:
2008-09-01
影响因子:
3.7
通讯作者:
Mori, Masaki
Mori, Masaki
中科院分区:
医学2区
文献类型:
--
作者:
Sakashita, Katsuya;Mimori, Koshi;Mori, Masaki

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背景:Tensin 4基因通过介导信号转导参与多种生物学事件。方法:收集114例胃癌患者的肿瘤组织和配对的正常胃黏膜标本,采用免疫组化方法检测胃癌组织中的p53、p54、p56、p53、p54、p56、p57、p58、p59、p50、p59、p510、p5提取总RNA,并使用实时逆转录聚合酶链反应定量TNS 4 mRNA表达。免疫组化法检测TNS 4蛋白表达。结果:肿瘤组织中TNS 4 mRNA的表达明显高于正常黏膜组织(P < 0.0001);进一步的免疫组化分析表明TNS 4蛋白主要在胃癌中表达。TNS 4 mRNA表达越高,肿瘤组织学分级越差(p < 0.02),浆膜浸润越深(p < 0.01),淋巴结转移(p < 0.02)或腹膜播散(p < 0.05)越多。TNS 4 mRNA高表达组患者的死亡率明显高于正常对照组(P < 0.05)。Kaplan-Meier曲线显示TNS 4高表达组患者的预后明显差于TNS 4低表达组(p < 0.01)。特别是2年总生存率分别为48.2%和83.1%,差异非常显著。多因素分析显示TNS 4 mRNA高表达是胃癌患者预后的独立预测因子(相对危险度1.41,95%可信区间1.03-1.96,p = 0.03)。TNS 4 mRNA的高表达可能是一种新的预后预测因子。
Background: The Tensin4 gene is involved in various biological events by mediating signal transduction. This study was designed to clarify its clinical significance in gastric cancer.Methods: Total of 114 gastric cancer patients were enrolled in this study, and we obtained paired samples from tumor tissue and matched normal mucosa. Total RNA was extracted, and TNS4 mRNA expression was quantified using real-time reverse-transcription polymerase chain reaction. TNS4 protein expression was investigated by immunohistochemistry. Additionally, the relationship between TNS4 expression and clinicopathologic factors was statistically analyzed.Results: TNS4 mRNA expression was significantly higher in tumor tissue than in normal mucosa (p < 0.0001). Additional immunohistochemical analysis demonstrated that TNS4 protein was predominantly expressed in gastric cancer. Tumors with higher TNS4 mRNA expression showed histologically poorer grade (p < 0.02), deeper invasion into the serosa (p < 0.01), more positive lymph node metastasis (p < 0.02) or peritoneal dissemination (p < 0.05). Patients with high TNS4 mRNA expression tumor were more likely to have cancer-related death (p < 0.05). A Kaplan-Meier curve also demonstrated that patients with high TNS4 expression tumor had significantly poorer prognosis (p < 0.01) than those with low TNS4 expression tumor. In particular, the 2-year overall survival rates were 48.2% and 83.1%, respectively, a very significant difference. Multivariate analysis revealed that high TNS4 mRNA expression was an independent prognostic predictor (relative risk 1.41, 95% confidence interval 1.03-1.96, p = 0.03).Conclusion: TNS4 was frequently overexpressed in gastric cancer, and tumors with high TNS4 mRNA expression showed biologically aggressive behavior. High TNS4 mRNA expression may be a novel prognostic predictor for those patients.