EP1-4 subtype, COX and PPARγ receptor expression in colorectal cancer in prediction of disease-specific mortality
EP1-4 subtype, COX and PPARγ receptor expression in colorectal cancer in prediction of disease-specific mortality
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DOI：
10.1002/ijc.22582
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发表时间：
2007-07-15
影响因子：
6.4
通讯作者：
Lundholm, Kent
中科院分区：
文献类型：
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作者：
Gustafsson, Annika;Hansson, Elisabeth;Lundholm, Kent
前列腺素在肿瘤生长和进展中的重要性已得到充分认识，包括环氧酶（COX）抑制剂的抗肿瘤活性。对COX抑制作用的治疗反应的变化质疑具有不同疾病进展的肿瘤中细胞表面和核膜受体表达的差异。这项研究的目的是评估结直肠癌中EP1-4亚型，PPAR伽马受体和COX-1/COX-2表达是否与肿瘤特异性死亡率有关。与正常结肠组织相比，使用逆转录聚合酶链反应和免疫组织化学在肿瘤组织中表现出表达和蛋白质外观。 EP1和EP2亚型受体蛋白在肿瘤细胞中高度存在，EP3偶尔发生，并且不可见EP4。与肿瘤组织相比，正常结肠组织中的PPAR伽马，EP2和EP4 mRNA明显更高，与公爵A-D肿瘤阶段没有任何明显的关系。多变量分析表明，增加的肿瘤组织EP2和COX-2表达预测存活率不佳（P <0.001）。在正常结肠组织中，COX-1表达显着高于COX-2表达。与正常结肠相比，肿瘤组织中的平均COX-2 mRNA并未增加。然而，大多数肿瘤细胞对COX-2蛋白染色阳性，Cox-2蛋白在正常粘膜细胞中低或无法检测到。 Cox-1蛋白在基质中优先可见。 EPI-4亚型受体mRNA通常与肿瘤组织中的COX-1和COX-2呈正相关，但在正常结肠中不相关。我们的结果表明，前列腺素的产生（COX-2）和通过EP1-4亚型受体（尤其是EP2）的信号传导预测了结直肠癌的疾病特异性死亡率（C）2007 Wiley-Liss，Inc.。
The importance of prostaglandins in tumor growth and progression is well recognized, including antineoplastic activities by cyclooxygenase (COX) inhibitors. Variation in treatment response to COX inhibition has questioned differences in expression of cell surface and nuclear membrane receptors among tumors with different disease progression. The purpose of this study was to evaluate whether EP1-4 subtype, PPAR gamma receptor and COX-1/COX-2 expression in colorectal cancer are related to tumor-specific mortality. Reverse transcription-polymerase chain reaction and immunohistochemistry were used to demonstrate expression and protein appearance in tumor tissue compared with normal colon tissue. EP1 and EP2 subtype receptor protein was highly present in tumor cells, EP3 occurred occasionally and EP4 was not visible. PPAR gamma, EP2 and EP4 mRNA were significantly higher in normal colon tissue compared with tumor tissue, without any distinct relationship to Dukes A-D tumor stage. Multivariate analyses indicated that increased tumor tissue EP2 and COX-2 expression predicted poor survival (p < 0.001). COX-1 expression was significantly higher than COX-2 expression in normal colon tissue. Average COX-2 mRNA was not increased in tumor tissue compared with normal colon. However, most tumor cells stained positive for COX-2 protein, which was low or undetectable in normal mucosa cells. COX-1 protein was preferentially visible in stroma. EPI-4 subtype receptor mRNAs were generally positively correlated to both COX-1 and COX-2 in tumor tissue, but not in normal colon. Our results imply that both prostaglandin production (COX-2) and signaling via EP1-4 subtype receptors, particularly EP2, predict disease-specific mortality in colorectal cancer (c) 2007 Wiley-Liss, Inc.