High ROR2 expression in tumor cells and stroma is correlated with poor prognosis in pancreatic ductal adenocarcinoma.
High ROR2 expression in tumor cells and stroma is correlated with poor prognosis in pancreatic ductal adenocarcinoma.
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DOI：
10.1038/srep12991
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发表时间：
2015-08-11
影响因子：
4.6
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Huang J;Fan X;Wang X;Lu Y;Zhu H;Wang W;Zhang S;Wang Z
RTK样孤儿受体2(ROR2)在多种肿瘤中高表达，具有致瘤活性。然而，ROR2在胰腺导管腺癌(PDAC)中的表达及其功能和预后意义尚不清楚。用实时荧光定量聚合酶链式反应检测肿瘤细胞系、相应瘤周组织和PDAC细胞系中ROR2基因的表达。应用免疫组织化学方法检测ROR2在PDAC中的表达，并探讨其与临床病理因素及预后的关系。PDAC组织中ROR2基因和蛋白的表达明显高于正常胰腺组织。癌细胞胞浆高表达与原发肿瘤、远处转移和TNM分期显著相关，间质高表达与区域淋巴结转移和TNM分期显著相关。Kaplan-Meier法和Cox回归分析显示，肿瘤胞浆或间质细胞中ROR2的高表达与PDAC的恶性程度和生存期显著相关。我们提出了强有力的证据表明，ROR2可以作为预后不良的指标，并可能成为PDAC的一个新的治疗靶点。
RTK-like orphan receptor 2 (ROR2) is overexpressed in several cancers and has tumorigenic activity. However, the expression of ROR2 and its functional and prognostic significance have yet to be evaluated in pancreatic ductal adenocarcinoma (PDAC). Quantitative real-time polymerase chain reaction was used to characterize the expression of ROR2 mRNA in PDAC, corresponding peritumoral tissues, and PDAC cell lines. Immunohistochemical analysis with tissue microarrays was used to evaluate ROR2 expression in PDAC and to investigate the relationship of this expression to clinicopathological factors and prognosis. The expression of ROR2 mRNA and protein was significantly higher in PDAC than in normal pancreatic tissues. High cytoplasmic ROR2 expression in cancer cells was significantly associated with a primary tumor, distant metastasis, and TNM stage, and high stromal ROR2 expression was significantly associated with regional lymph node metastasis and TNM stage. The Kaplan–Meier method and Cox regression analyses showed that high ROR2 expression in tumor cytoplasm or stromal cells was significantly associated with malignant attributes and reduced survival in PDAC. We present strong evidence that ROR2 could be used as an indicator of poor prognosis and could represent a novel therapeutic target for PDAC.