Reduction of 15-hydroxyprostaglandin dehydrogenase expression is an independent predictor of poor survival associated with enhanced cell proliferation in gastric adenocarcinoma
Reduction of 15-hydroxyprostaglandin dehydrogenase expression is an independent predictor of poor survival associated with enhanced cell proliferation in gastric adenocarcinoma
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DOI：
10.1111/j.1349-7006.2009.01390.x
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发表时间：
2010-02-01
期刊：
影响因子：
5.7
通讯作者：
Arakawa, Tetsuo
中科院分区：
文献类型：
--
作者：
Tatsuwaki, Hiroshi;Tanigawa, Tetsuya;Arakawa, Tetsuo
前列腺素（PG） E-2促进胃肠道癌变和肿瘤进展。我们确定了胃腺癌中15-羟基前列腺素脱氢酶（15-PGDH）的表达模式与各种临床病理因素和患者预后之间的相关性(2)，试图阐明其生物学意义。15-羟基前列腺素脱氢酶是一种降解PGE生物失活的酶。71例胃腺癌中有35例肿瘤组织中15-PGDH蛋白表达降低。多变量分析显示15-PGDH表达减少是生存不良的独立预测因子。15- pgdh阴性腺癌中ki67阳性细胞比例高于15- pgdh阳性腺癌。环氧化酶2 （COX-2）阳性肿瘤患者的临床病理参数与COX-2阴性肿瘤患者的临床病理参数无差异。在一项体外研究中，在表达15-PGDH的胃癌细胞系AGS中，使用特异性siRNA沉默15-PGDH或15-PGDH特异性抑制剂可增强细胞增殖。这些发现表明，15-PGDH的减少是胃腺癌中与细胞增殖增强相关的生存不良的独立预测因子。（癌症科学2010；101:550-558）
Prostaglandin (PG) E-2 promotes gastrointestinal carcinogenesis and tumor progression. We determined the correlations between pattern of expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a catabolic enzyme for biological inactivation of PGE(2), in gastric adenocarcinoma and various clinicopathological factors and patient outcome in an attempt to elucidate its biological significance. In 35 of 71 cases of gastric adenocarcinoma, expression of 15-PGDH protein was reduced in tumor tissues. Multivariate analysis revealed reduction of 15-PGDH expression to be an independent predictor of poor survival. The proportion of Ki67-positive cells in 15-PGDH-negative adenocarcinoma was higher than that in 15-PGDH-positive adenocarcinoma. No differences were found in clinicopathological parameters between patients with cyclooxygenase-2 (COX-2)-positive tumors and those with COX-2 negative tumors. In an in vitro study, use of specific siRNA to silence 15-PGDH or a specific inhibitor of 15-PGDH enhanced cell proliferation in the gastric cancer cell line AGS, which expresses 15-PGDH. These findings suggest that reduction of 15-PGDH is an independent predictor of poor survival associated with enhancement of cell proliferation in gastric adenocarcinoma. (Cancer Sci 2010; 101: 550-558)