Sakashita Katsuya, Mimori Koshi, Tanaka Fumiaki, Kamohara Yukio, Inoue Hiroshi, Sawada Tetsuji, Hirakawa Kosei, Mori Masaki
Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan.
Ann Surg Oncol. 2008 Sep;15(9):2606-13. doi: 10.1245/s10434-008-9989-8. Epub 2008 Jul 9.
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.
A 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.
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).
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.
张力蛋白4（Tensin4）基因通过介导信号转导参与多种生物学事件。本研究旨在阐明其在胃癌中的临床意义。
本研究共纳入114例胃癌患者，我们从肿瘤组织和配对的正常黏膜中获取样本。提取总RNA，使用实时逆转录聚合酶链反应定量TNS4 mRNA表达。通过免疫组织化学研究TNS4蛋白表达。此外，对TNS4表达与临床病理因素之间的关系进行统计学分析。
TNS4 mRNA在肿瘤组织中的表达显著高于正常黏膜（p < 0.0001）。进一步的免疫组织化学分析表明，TNS4蛋白主要在胃癌中表达。TNS4 mRNA表达较高的肿瘤在组织学上分级较差（p < 0.02），侵犯浆膜更深（p < 0.01），淋巴结转移更阳性（p < 0.02）或腹膜播散更明显（p < 0.05）。TNS4 mRNA表达高的肿瘤患者更易发生癌症相关死亡（p < 0.05）。Kaplan-Meier曲线也表明，TNS4表达高的肿瘤患者的预后明显比TNS4表达低的肿瘤患者差（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，TNS4 mRNA高表达是一个独立的预后预测指标（相对风险1.41，95%置信区间1.03 - 1.96，p = 0.03）。
TNS4在胃癌中经常过度表达，TNS4 mRNA表达高的肿瘤表现出生物学侵袭性行为。TNS4 mRNA高表达可能是这些患者的一个新的预后预测指标。
