ROR2 is a novel prognostic biomarker and a potential therapeutic target in leiomyosarcoma and gastrointestinal stromal tumour.
ROR2 is a novel prognostic biomarker and a potential therapeutic target in leiomyosarcoma and gastrointestinal stromal tumour.
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DOI：
10.1002/path.3986
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发表时间：
2012-06
影响因子：
7.3
通讯作者：
van de Rijn, Matt
中科院分区：
文献类型：
--
作者：
Edris, Badreddin;Espinosa, Inigo;Muehlenberg, Thomas;Mikels, Amanda;Lee, Cheng-Han;Steigen, Sonja E.;Zhu, Shirley;Montgomery, Kelli D.;Lazar, Alexander J. F.;Lev, Dina;Fletcher, Jonathan A.;Beck, Andrew H.;West, Robert B.;Nusse, Roel;van de Rijn, Matt
软组织肉瘤是一组恶性肿瘤，其临床管理复杂的形态异质性，不足的分子标记物和有限的治疗选择。受体酪氨酸激酶（RTK）已被证明在癌症中发挥重要作用，既作为治疗靶点，也作为预后生物标志物。对148例肉瘤中48个RTK基因表达数据的初步筛选显示，ROR2在平滑肌肉瘤（LMS）、胃肠道间质瘤（GIST）和韧带样型纤维瘤病（DTF）的一个亚组中表达。这进一步证实了免疫组织化学（IHC）的573个组织样本从59肉瘤肿瘤类型。在这里，我们提供的证据表明，ROR2的表达发挥作用的LMS和GIST细胞在体外的侵袭能力。我们还表明，敲低ROR2显着降低肿瘤质量在体内使用异种移植模型的LMS。最后，我们表明，ROR2的表达，如通过IHC测量，预测与LMS和GIST患者的临床结果差，虽然它不是独立的其他临床病理特征在多变量分析，和ROR2表达之间保持原发性肿瘤和它们的转移。总之，这些结果表明，ROR2是一个有用的预后指标，在这些软组织肉瘤的临床管理，并可能代表一个新的治疗靶点。
Soft-tissue sarcomas are a group of malignant tumours whose clinical management is complicated by morphological heterogeneity, inadequate molecular markers and limited therapeutic options. Receptor tyrosine kinases (RTKs) have been shown to play important roles in cancer, both as therapeutic targets and as prognostic biomarkers. An initial screen of gene expression data for 48 RTKs in 148 sarcomas showed that ROR2 was expressed in a subset of leiomyosarcoma (LMS), gastrointestinal stromal tumour (GIST) and desmoid-type fibromatosis (DTF). This was further confirmed by immunohistochemistry (IHC) on 573 tissue samples from 59 sarcoma tumour types. Here we provide evidence that ROR2 expression plays a role in the invasive abilities of LMS and GIST cells in vitro. We also show that knockdown of ROR2 significantly reduces tumour mass in vivo using a xenotransplantation model of LMS. Lastly, we show that ROR2 expression, as measured by IHC, predicts poor clinical outcome in patients with LMS and GIST, although it was not independent of other clinico-pathological features in a multivariate analysis, and that ROR2 expression is maintained between primary tumours and their metastases. Together, these results show that ROR2 is a useful prognostic indicator in the clinical management of these soft-tissue sarcomas and may represent a novel therapeutic target.
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DOI：
10.1073/pnas.96.16.9212
发表时间：
1999-08-03
影响因子：
11.1
作者：
Perou, CM;Jeffrey, SS;Botstein, D
通讯作者：
Botstein, D
影响因子：
2.1
作者：
Oishi, I;Suzuki, H;Minami, Y
通讯作者：
Minami, Y
影响因子：
8
作者：
Wright, T. M.;Brannon, A. R.;Gordan, J. D.;Mikels, A. J.;Mitchell, C.;Chen, S.;Espinosa, I.;van de Rijn, M.;Pruthi, R.;Wallen, E.;Edwards, L.;Nusse, R.;Rathmell, W. K.
通讯作者：
Rathmell, W. K.
影响因子：
7.5
作者：
Steigen, Sonja E.;Bjerkehagen, Bodil;Nielsen, Torsten O.
通讯作者：
Nielsen, Torsten O.
影响因子：
6
作者：
Lazar, Alexander J. F.;Tuvin, Daniel;Lev, Dina
通讯作者：
Lev, Dina