Expression of ROR1 has prognostic significance in triple negative breast cancer

Abstract

Overexpression of receptor tyrosine kinase-like orphan receptor (ROR1) in a variety of human malignancies is associated with aggressive behaviour. Therapeutic agents targeting ROR1 have shown promising results in vivo and in vitro studies. In breast cancer, high-level expression of ROR1 mRNA is associated with high-grade tumours and metastasis. We investigated the prevalence and prognostic significance of ROR1 expression in triple negative breast cancer (TNBC). ROR1 was immunohistochemically stained on full-face sections of 210 TNBC patient samples. Forty-seven TNBC cases (22.4 %) showed strong ROR1 expression, which was associated with shorter disease-free survival (DFS; P = 0.00015), distant metastasis-free survival (DMFS; P = 0.00013) and overall survival (OS; P = 0.026) in univariate analyses. Results were confirmed by multivariate analysis. Seventy TNBC cases (33.3 %) with medullary features showed longer OS (P = 0.00013). We divided the whole series into two subgroups based on the presence or absence of medullary features. Strong ROR1 expression retained a predictive value of shorter DFS and DMFS in both subgroups. Our study suggests that strong ROR1 expression might be an independent adverse prognostic factor in TNBC patients and may serve as a potential marker for patient selection in ROR1-targeted therapy. More large-scale studies are needed to clarify its potential usefulness.

High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia

“…A variety of different cancers have been found to express ROR1. 23 To date, high-level expression of ROR1 has been found to have adverse prognostic significance for patients with breast cancer, [24][25][26][27] ovarian cancer, 28,29 melanoma, 30 or Ewing sarcoma. 31 Moreover, high-level expression of ROR1 also has been associated with higher levels of AKT activation, 24,30,32,33 consistent with the notion that ROR1 signaling leading to activation of AKT may serve as a driver, not just in CLL, but also in other malignancies.…”

A ROR1–HER3–lncRNA signalling axis modulates the Hippo–YAP pathway to regulate bone metastasis

“…The two ROR family members, ROR1 and ROR2, were originally found to be involved in skeletal, cardiorespiratory, and neurological development 15,16 . Rising evidence has indicated that both ROR proteins are highly expressed in multiple human cancer types, including leukemia, ovarian cancer, and breast cancer 17–22 . Although ROR1 treated as a pseudokinase originally based on the observation that ROR1 was unable to be autophosphorylated 23,24 , some studies have also demonstrated the moderate autocatalytic kinase activity of ROR1 in vitro 25–27 .…”

Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer

“…It is recognized that ROR1 and ROR2 expression diminishes in adult tissue [27], with many studies indicating increased expression associated with malignant progression [3], [4], [10], [11], [12], [28], [29], [30]. We have previously found ROR2 and its receptor, WNT5A, to be upregulated in OC [13], [31], [32] patient samples and have shown in vitro that both ROR1 and ROR2 are important in OC migration and invasion, indicating a role in OC metastasis [32].…”

“…In many cases, the receptor tyrosine kinases ROR1 and ROR2 are abnormally overexpressed in tumors and associated with stem cell properties, epithelial to mesenchymal transition, and metastasis [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]. In OC, we have previously shown that both ROR1 and ROR2 are important in cell growth, migration, and invasion [13].…”