Clinical Significance of Low Expression of Prostasin mRNA in Human Gastric Cancer
Clinical Significance of Low Expression of Prostasin mRNA in Human Gastric Cancer
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DOI：
10.1002/jso.21158
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发表时间：
2008-12-01
影响因子：
2.5
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Sakashita, Katsuya;Mimori, Koshi;Mori, Masaki
背景：前列腺素被认为具有抑制肿瘤进展的活性。方法：收集108例胃癌患者的肿瘤组织及相应的正常组织标本，采用免疫组化法检测胃癌组织中的p53蛋白表达。采用真实的时间反转录-聚合酶链反应（RT-PCR）和免疫组化方法检测前列腺素的表达。通过去甲基化处理来检查表达的表观遗传沉默。Kaplan-Meier曲线分析生存率，并分析其表达与临床病理因素的关系。免疫组化证实前列腺素在胃癌中表达缺失。不表达前列腺素mRNA的胃癌细胞系在去甲基化处理后恢复其表达。在那些肿瘤表达前列腺素mRNA水平降低的患者中，我们观察到较短的生存期（P=0.0110），这是由于淋巴结转移（P = 0.0087）、淋巴渗透（P = 0.0542）结论：前列腺素mRNA在胃癌组织中表达下调。表达缺失可能受表观遗传因素调节，导致生存期缩短。前列腺素mRNA表达降低可能是胃癌生物学侵袭性的一个新指标。
Background: Prostasin is considered to have Suppressive activities against tumor progression. The aim of this study was to clarify its Clinical significance in gastric cancer.Methods: Tumor and the corresponding normal samples were prepared from a total of 108 gastric cancer patients. Prostasin expression was assayed by real time reverse transcription (RT)-polymerase chain reaction (PCR) and by immunohistochemistry. Epigenetic silencing of the expression was examined by demethylation treatment. Survival was examined in Kaplan-Meier plots, and the relationship between its expression and clinicopathologic factors was statistically analyzed.Results: Prostasin mRNA expression was significantly down-regulated in tumor tissues. Immunohistochemistry confirmed loss of Prostasin expression in gastric cancer. Gastric cancer cell lines that did not express Prostasin mRNA retrieved its expression following demethylation treatment. In those patients whose tumor expressed Prostasin mRNA at reduced levels, we observed shorter survival (P=0.0110), due to a higher incidence of lymph node metastasis (P = 0.0087), lymphatic permeation (P = 0.0542.) and venous permeation (P = 0.0492).Conclusions: Prostasin mRNA expression was frequently down-regulated in gastric cancer. Loss of expression might be regulated by epigenetic factors, contributing to the shorter survival. Reduced Prostasin mRNA expression might be a novel indicator for biological aggressiveness in gastric cancer.