Cyclooxygenase-2 expression in human colorectal cancer is unrelated to overall patient survival
Cyclooxygenase-2 expression in human colorectal cancer is unrelated to overall patient survival
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DOI：
10.1158/1078-0432.ccr-04-2586
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发表时间：
2005-07-01
影响因子：
11.5
通讯作者：
Fritz, P
中科院分区：
文献类型：
--
作者：
Fux, R;Schwab, M;Fritz, P
目的：环加氧酶-2 (COX-2) 在人类结直肠癌和腺瘤组织中的表达似乎高于正常粘膜。然而，关于 COX-2 表达与患者生存之间关系的数据尚无定论。因此，我们研究了747例结直肠癌患者的手术组织中COX-2的表达和生存时间。 实验设计：对747例原发性结直肠癌手术标本进行COX-2免疫染色，并在透射光显微镜下进行评估，根据染色的强度和程度对COX-2表达进行评分，得出COX-2免疫反应性评分（IRS-COX2）。分析了 IRS-COX2 所有可能的截止点，以确定 COX-2 表达与患者生存之间的关系。 结果：单变量和多变量分析均表明，无论 IRS-COX2 的截止点如何，人肿瘤上皮细胞中的 COX-2 表达与患者总体生存率和无病生存率无关。 1年、3年、5年和10年的生存率分别为81.0%、66.8%、60.2%和49.8%（中位：117.3个月；95%置信区间，102.3-132.0）。在多变量分析中，只有淋巴结和转移与患者总体生存率显着相关。当IV期和直肠癌患者被排除在分析之外时，得到了类似的结果。结论：肿瘤上皮细胞中COX-2的表达似乎与结直肠癌患者的生存无关。除 COX-2 外，还有几个靶点，例如过氧化物酶体增殖物激活受体，与癌发生有关，并且可能受到非甾体抗炎药的调节。需要进一步的研究来确定它们的预后相关性。
Purpose: Cyclooxygenase-2 (COX-2) expression in human colorectal cancer and adenoma tissue seems to be higher than in normal mucosa. However, data about the relation between COX-2 expression and patient survival are inconclusive as yet. Therefore, we studied COX-2 expression in surgery tissue and survival time in a cohort of 747 colorectal cancer patients.Experimental Design: Surgical specimens of primary colorectal cancer from 747 individuals were immunostained for COX-2 and evaluated under a transmission light microscope, COX-2 expression was scored according to intensity and extent of staining, resulting in the COX-2 immunoreactivity score (IRS-COX2). All possible cutoff points for IRS-COX2 were analyzed for a relation between COX-2 expression and patient survival.Results: Both univariable and multivariable analysis have shown that the COX-2 expression in human tumor epithelial cells was unrelated to overall patient survival and to disease-free survival, irrespectively of the cutoff point for IRS-COX2. The survival rates for 1, 3, 5, and 10 years were 81.0%, 66.8%, 60.2%, and 49.8% (median: 117.3 months; 95% confidence interval, 102.3-132.0), respectively. In the multivariable analysis, only node and metastasis were significantly related to overall patient survival. Similar results were obtained when stage IV and rectal cancer patients were excluded from the analysis.Conclusions: COX-2 expression in tumor epithelial cells does not seem to be related to survival of colorectal cancer patients. Besides COX-2, there are several targets, such as the peroxisome proliferator-activated receptors, that are involved in carcinogenesis and may be modulated by nonsteroidal anti-inflammatory drugs. Further studies are needed to determine their prognostic relevance.