背景:Wnt5a是非经典Wnt途径的关键配体,受体酪氨酸激酶样孤儿受体2(ROR2)是与Wnt5a相关的受体。非经典Wnt信号通路与肝细胞癌(HCC)癌变之间的关联尚不清楚。本研究探讨了ROR2在HCC中表达的意义。
方法:本研究检测了ROR2在肝癌细胞系中的表达。对243例切除的HCC标本进行ROR2的免疫组织化学染色。本研究探讨了ROR2的表达及其与临床病理因素和预后的关系。
结果:研究结果表明,ROR2在分化良好的Huh7和HepG2细胞中表达,但不在低分化的HLE和HLF细胞中。ROR2在147例(60.5%)肝癌标本中呈阳性表达,在96例(39.5%)肝癌标本中呈阴性表达。ROR2阴性与高甲胎蛋白(AFP)水平之间存在显着关联(P=0.006),分化差(P=0.015),Wnt5a阴性(P=0.024)。ROR2阴性组的5年总生存率(OS)(64.2%)比ROR2阳性组(73.8%)更差。但差异不显著(P=0.312)。ROR2+Wnt5a+组5年OS率为78.7%,ROR2+Wnt5a-组71.3%,ROR2-Wnt5a+组的80.8%,ROR2-Wnt5a-组为60.5%。ROR2-Wnt5a-组的OS显著低于ROR2+Wnt5a+组(P=0.030)。多因素分析显示,Wnt5a-ROR2-是一个独立的预后因素(风险比,2.058;95%置信区间,1.013-4.180;P=0.045)。
结论:ROR2和Wnt5a的联合可能是HCC的预后指标。Wnt5a/ROR2信号通路可能参与HCC的分化。该通路可能是HCC新的治疗靶点。
BACKGROUND: Wnt5a is the key ligand of the noncanonical Wnt pathway, and receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a receptor associated with Wnt5a. The association between the noncanonical Wnt-signaling pathway and carcinogenesis in hepatocellular carcinoma (HCC) is unclear. This study investigated the significance of
ROR2 expression in HCC.
METHODS: The study examined ROR2 expression in liver cancer cell lines. Immunohistochemical staining of ROR2 was performed on 243 resected HCC specimens. The study investigated ROR2 expression and its association with clinicopathologic factors and prognosis.
RESULTS: Findings showed that ROR2 was expressed in well-differentiated Huh7 and HepG2 cells, but not in poorly differentiated HLE and HLF cells. Expression of ROR2 was positive in 147 (60.5%) and negative in 96 (39.5%) HCC specimens. A significant association was shown between ROR2 negativity and high alpha-fetoprotein (AFP) level (P = 0.006), poor differentiation (P = 0.015), and Wnt5a negativity (P = 0.024). The 5-year overall survival (OS) rate for the ROR2-negative group (64.2 %) tended to be worse than for the ROR2-positive group (73.8%), but the difference was not significant (P = 0.312). The 5-year OS rate was 78.7% for the
ROR2+Wnt5a+ group, 71.3 % for the
ROR2+Wnt5a- group, 80.8% for the
ROR2-Wnt5a+ group, and 60.5 % for the
ROR2-Wnt5a- group. The OS in the
ROR2-Wnt5a- group was significantly poorer than in the
ROR2+Wnt5a+ group (P = 0.030). The multivariate analysis showed that Wnt5a-ROR2- was an independent prognostic factor (hazard ratio, 2.058; 95% confidence interval, 1.013-4.180; P = 0.045).
CONCLUSIONS: The combination of ROR2 and Wnt5a may be a prognostic indicator for HCC. The Wnt5a/
ROR2 signal pathway may be involved in the differentiation of HCC. This pathway may be a new therapeutic target for HCC.