Up-Regulation of Cadherin 17 and Down-Regulation of Homeodomain Protein CDX2 Correlate With Tumor Progression and Unfavorable Prognosis in Epithelial Ovarian Cancer
Up-Regulation of Cadherin 17 and Down-Regulation of Homeodomain Protein CDX2 Correlate With Tumor Progression and Unfavorable Prognosis in Epithelial Ovarian Cancer
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DOI：
10.1097/igc.0b013e318261d89c
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发表时间：
2012-09-01
影响因子：
4.8
通讯作者：
Wang, Sui-Hai
中科院分区：
文献类型：
--
作者：
Huang, Li-Ping;Yu, Yan-Hong;Wang, Sui-Hai
目的：钙粘蛋白17（CDH17）属于7D-钙粘蛋白超家族，是一种新型癌基因，参与肿瘤的侵袭和转移。其表达已被证明受到尾部相关同源盒转录因子 CDX2 的调节。对两种生物标志物的作用的解释是相互矛盾的。因此，本研究的目的是探讨CDH17和CDX2在人上皮性卵巢癌（EOC）中的表达模式，并评估这2种标志物在EOC进展和预后中的临床意义。方法：采用免疫组化染色法检测182例石蜡包埋EOC标本中CDH17和CDX2的表达。统计分析其表达与临床病理因素及总生存期的关系。结果：与正常卵巢表面上皮组织相比，EOC组织中CDH17表达上调，CDX2表达下调。 EOC组织中CDH17和CDX2表达呈负相关（r = -0.76，P = 0.001）。 CDH17 高表达的肿瘤更有可能处于晚期 (P = 0.01) 和更高级别 (P = 0.03)。 CDX2 表达低的患者更容易处于疾病晚期 (P = 0.01)。此外，单变量分析表明，CDH17 高表达的患者与 EOC 患者的不良预后相关（P = 0.001），而 CDX2 表达高的患者则与不良预后相关（P = 0.003）。尤其是CDH17高/CDX2低表达的EOC患者生存率最低（P < 0.001）。多因素统计分析显示CDH17/CDX2联合表达是EOC的独立预后指标（P = 0.01）。结论：我们的数据提示CDH17的上调和CDX2的下调可能与EOC的晚期阶段相关。 CDH17/CDX2 表达的联合检测可能与该疾病患者的不良预后相关。
Objective: Cadherin 17 (CDH17), belonging to the 7D-cadherin superfamily, represents a novel oncogene, which is involved in tumor invasion and metastasis. Its expression has been demonstrated to be regulated by caudal-related homeobox transcription factor CDX2. The roles of 2 biomarkers have been conflictingly explained. Therefore, the aims of this study were to investigate the expression patterns of CDH17 and CDX2 in human epithelial ovarian cancer (EOC) and to evaluate the clinical significance of these 2 markers in the progression and prognosis of EOC.Methods: CDH17 and CDX2 expressions in 182 paraffin-embedded EOC specimens were detected by immunohistochemical staining. Associations of their expression with clinical pathological factors and overall survival were statistically evaluated.Results: Compared with normal surface ovarian epithelium tissues, CDH17 expression was upregulated and CDX2 expression was downregulated in EOC tissues. There was a negative correlation between CDH17 and CDX2 expression in EOC tissues (r = -0.76, P = 0.001). Tumors with high CDH17 expression were more likely to have advanced stage (P = 0.01) and higher grade (P = 0.03). Patients with low CDX2 expression were more frequently to be at the advanced stage of disease (P = 0.01). In addition, univariate analysis indicated that the patients with high CDH17 expression correlated with poor prognosis in patients with EOC (P = 0.001), as opposed to CDX2 (P = 0.003). Especially, the survival rate of patients with EOC with CDH17-high/CDX2-low expression was the lowest (P < 0.001). Multivariate statistical analysis showed that the conjoined expression of CDH17/CDX2 was an independent prognostic indicator of EOC (P = 0.01).Conclusions: Our data suggest that both the up-regulation of CDH17 and the down-regulation of CDX2 may be associated with the advanced stage of EOC. A conjoined detection of CDH17/CDX2 expression may be associated with unfavorable prognosis in patients with this disease.