Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
Medicines Policy Research Unit, Centre for Big Data Research in Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.
Sci Rep. 2020 Aug 17;10(1):13906. doi: 10.1038/s41598-020-70924-z.
ROR1 and ROR2 are receptor tyrosine kinases with altered expression in a range of cancers. Silencing ROR1 or ROR2 in different tumour types has been shown to inhibit proliferation and decrease metastatic potential. The aim of this study was to investigate the role of ROR1 and ROR2 in endometrial cancer via immunohistochemistry (IHC) in a large endometrial cancer patient cohort (n = 499) and through in vitro analysis in endometrial cancer cell lines. Correlation was assessed between ROR1/2 expression and clinicopathological parameters. Kaplan Meier curves were produced for 5-year progression free survival (PFS) and overall survival (OS) with low/moderate versus high ROR1/2 intensity. Cox multivariate regression was applied to analyse the effect of selected covariates on the PFS and OS. The effect of ROR1 and/or ROR2 modulation on cell proliferation, adhesion, migration and invasion was analysed in two endometrial cancer cell lines (KLE and MFE-296). We observed a significant decrease in OS and PFS in patients with high ROR1 expression. ROR1 silencing and ROR2 overexpression significantly inhibited proliferation of KLE endometrial cancer cells and decreased migration. This study supports the oncogenic role of ROR1 in endometrial cancer, and warrants investigation of future application of ROR1-targeting therapies in endometrial cancer patients.
ROR1 和 ROR2 是受体酪氨酸激酶，在多种癌症中表达异常。在不同肿瘤类型中沉默 ROR1 或 ROR2 已被证明可抑制增殖并降低转移潜能。本研究旨在通过对 499 例大型子宫内膜癌患者队列进行免疫组织化学（IHC）分析，以及在子宫内膜癌细胞系中进行体外分析，来研究 ROR1 和 ROR2 在子宫内膜癌中的作用。评估了 ROR1/2 表达与临床病理参数之间的相关性。绘制了 5 年无进展生存（PFS）和总生存（OS）的 Kaplan-Meier 曲线，低/中度与高 ROR1/2 强度相比。应用 Cox 多变量回归分析了选定协变量对 PFS 和 OS 的影响。在两种子宫内膜癌细胞系（KLE 和 MFE-296）中分析了 ROR1 和/或 ROR2 调节对细胞增殖、粘附、迁移和侵袭的影响。我们观察到高 ROR1 表达的患者 OS 和 PFS 显著降低。ROR1 沉默和 ROR2 过表达显著抑制了 KLE 子宫内膜癌细胞的增殖并减少了迁移。这项研究支持 ROR1 在子宫内膜癌中的致癌作用，并需要进一步研究 ROR1 靶向治疗在子宫内膜癌患者中的应用。
