Wang Hao-Wei, Hsueh Chung-Tsen, Lin Chien-Fu Jeff, Chou Teh-Ying, Hsu Wen-Hu, Wang Liang-Shun, Wu Yu-Chung
Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, 201, Sec 2, Shih-Pai Road, Taipei 112, Taiwan.
Ann Surg Oncol. 2006 Sep;13(9):1224-34. doi: 10.1245/s10434-006-9001-4. Epub 2006 Sep 3.
Microsomal prostaglandin E synthase-1 (mPGES-1) has recently been found to overexpress in human cancers, including non-small-cell lung cancer (NSCLC). However, the clinical value is largely unknown. The aim of this study was to investigate the associations between mPGES-1 expression in NSCLC and the clinical characteristics and survival outcome.
Between 2001 and 2003, paired fresh tumorous and nontumorous samples were prospectively procured from patients undergoing surgery for NSCLC. The expression of mPGES-1 was assessed by using Western blot in 93 subjects and reverse transcriptase-polymerase chain reaction in 35. Overexpression of mPGES-1 was defined as a more than 2-fold expression in the tumorous sample compared with the corresponding nontumorous one. Immunohistochemistry was used to confirm its localization to the tumor cells. In a subset of 30 cases, cyclooxygenase-2 (COX-2) was also analyzed to assess its association with mPGES-1.
The protein and messenger RNA of mPGES-1 were both expressed at higher levels in the tumor samples (P < .001 and P = .006, respectively). The expressions of mPGES-1 and COX-2 were unrelated (P = .715). Overexpression of mPGES-1 protein was observed in 61 (65.6%) of 93 patients, but it was not significantly associated with the clinicopathologic characteristics or overall and disease-free survivals. However, mPGES-1 overexpression seemed to be associated with the likelihood of subsequent pulmonary metastases and a lower tendency for developing bony metastases (P = .001 and P = .006, respectively).
Our results demonstrated that mPGES-1 was overexpressed in NSCLC, unassociated with COX-2. Overexpression of mPGES-1 per se was not a prognostic indicator, but it might be implicated in the organ preference of metastasis.
微粒体前列腺素E合酶-1(mPGES-1)最近被发现在包括非小细胞肺癌(NSCLC)在内的人类癌症中过度表达。然而,其临床价值在很大程度上尚不清楚。本研究的目的是探讨NSCLC中mPGES-1表达与临床特征及生存结果之间的关联。
在2001年至2003年期间,前瞻性地从接受NSCLC手术的患者中获取配对的新鲜肿瘤和非肿瘤样本。采用蛋白质印迹法对93名受试者的mPGES-1表达进行评估,采用逆转录聚合酶链反应对35名受试者进行评估。mPGES-1的过度表达定义为肿瘤样本中的表达比相应的非肿瘤样本高2倍以上。采用免疫组织化学法确认其在肿瘤细胞中的定位。在30例患者的子集中,还分析了环氧合酶-2(COX-2)以评估其与mPGES-1的关联。
mPGES-1的蛋白质和信使核糖核酸在肿瘤样本中的表达均较高(分别为P <.001和P =.006)。mPGES-1和COX-2的表达无关(P =.715)。在93例患者中的61例(65.6%)中观察到mPGES-1蛋白的过度表达,但它与临床病理特征、总生存期和无病生存期均无显著关联。然而,mPGES-1的过度表达似乎与随后发生肺转移的可能性以及发生骨转移的较低倾向相关(分别为P =.001和P =.006)。
我们的结果表明,mPGES-1在NSCLC中过度表达,与COX-2无关。mPGES-1的过度表达本身不是一个预后指标,但它可能与转移的器官偏好有关。