Prognostic Significance of ROR2 Expression in Patients with Urothelial Carcinoma

We investigated the association of receptor tyrosine kinase-like orphan receptor 2 (ROR2) expression with clinicopathological features and oncologic outcomes in large urothelial carcinoma (UC) of the upper tract (UTUC) and urinary bladder (UBUC) cohorts. Through transcriptomic profiling of a publish...

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Main Authors: Cheng-Fa Yeh, Ti-Chun Chan, Hung-Lung Ke, Tzu-Ju Chen, Li-Ching Wu, Hsiang-Ying Lee, Yu-Ching Wei, Wen-Jeng Wu, Chien-Feng Li, Wei-Ming Li
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/9/8/1054
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author Cheng-Fa Yeh
Ti-Chun Chan
Hung-Lung Ke
Tzu-Ju Chen
Li-Ching Wu
Hsiang-Ying Lee
Yu-Ching Wei
Wen-Jeng Wu
Chien-Feng Li
Wei-Ming Li
author_facet Cheng-Fa Yeh
Ti-Chun Chan
Hung-Lung Ke
Tzu-Ju Chen
Li-Ching Wu
Hsiang-Ying Lee
Yu-Ching Wei
Wen-Jeng Wu
Chien-Feng Li
Wei-Ming Li
author_sort Cheng-Fa Yeh
collection DOAJ
description We investigated the association of receptor tyrosine kinase-like orphan receptor 2 (ROR2) expression with clinicopathological features and oncologic outcomes in large urothelial carcinoma (UC) of the upper tract (UTUC) and urinary bladder (UBUC) cohorts. Through transcriptomic profiling of a published dataset (GSE31684), ROR2 was discovered to be the most upregulated gene during UC progression, focusing on the JNK cascade (GO:0007254). Initially, the evaluation of <i>ROR2</i> mRNA expression in 50 frozen UBUCs showed significantly upregulated levels in high-stage UC. Moreover, high ROR2 immunoexpression significantly correlated with high tumor stage, high tumor grade, lymph node metastasis, and vascular invasion (all <i>p</i> < 0.05). In multivariate analysis, after adjusting for standard clinicopathological features, ROR2 expression status was an independent prognosticator of cancer-specific survival and metastasis-free survival in UTUC and UBUC (all <i>p</i> < 0.01). In the subgroup analysis, it also significantly predicted bladder tumor recurrence in non-muscle invasive UBUC. Furthermore, the GO enrichment analysis showed that fatty acid, monocarboxylic acid, carboxylic acid metabolic processes, negative regulation of neutrophil migration, and negative regulation of granulocyte and neutrophil chemotaxis were significantly enriched by ROR2 dysregulation. In conclusion, high ROR2 immunoexpression was associated with aggressive pathological characteristics in UC and independently predicted worse prognosis, suggesting it could play roles in clinical risk stratification and therapy decisions.
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spelling doaj.art-9b3fe8e435864d55b9551a8b4c04dbb52023-11-22T06:54:01ZengMDPI AGBiomedicines2227-90592021-08-0198105410.3390/biomedicines9081054Prognostic Significance of ROR2 Expression in Patients with Urothelial CarcinomaCheng-Fa Yeh0Ti-Chun Chan1Hung-Lung Ke2Tzu-Ju Chen3Li-Ching Wu4Hsiang-Ying Lee5Yu-Ching Wei6Wen-Jeng Wu7Chien-Feng Li8Wei-Ming Li9Division of General Internal Medicine, Chi Mei Medical Center, Tainan 710, TaiwanDepartment of Medical Research, Chi Mei Medical Center, Tainan 710, TaiwanDepartment of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDepartment of Clinical Pathology, Chi Mei Medical Center, Tainan 710, TaiwanDepartment of Clinical Pathology, Chi Mei Medical Center, Tainan 710, TaiwanDepartment of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDepartment of Pathology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDepartment of Medical Research, Chi Mei Medical Center, Tainan 710, TaiwanDepartment of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanWe investigated the association of receptor tyrosine kinase-like orphan receptor 2 (ROR2) expression with clinicopathological features and oncologic outcomes in large urothelial carcinoma (UC) of the upper tract (UTUC) and urinary bladder (UBUC) cohorts. Through transcriptomic profiling of a published dataset (GSE31684), ROR2 was discovered to be the most upregulated gene during UC progression, focusing on the JNK cascade (GO:0007254). Initially, the evaluation of <i>ROR2</i> mRNA expression in 50 frozen UBUCs showed significantly upregulated levels in high-stage UC. Moreover, high ROR2 immunoexpression significantly correlated with high tumor stage, high tumor grade, lymph node metastasis, and vascular invasion (all <i>p</i> < 0.05). In multivariate analysis, after adjusting for standard clinicopathological features, ROR2 expression status was an independent prognosticator of cancer-specific survival and metastasis-free survival in UTUC and UBUC (all <i>p</i> < 0.01). In the subgroup analysis, it also significantly predicted bladder tumor recurrence in non-muscle invasive UBUC. Furthermore, the GO enrichment analysis showed that fatty acid, monocarboxylic acid, carboxylic acid metabolic processes, negative regulation of neutrophil migration, and negative regulation of granulocyte and neutrophil chemotaxis were significantly enriched by ROR2 dysregulation. In conclusion, high ROR2 immunoexpression was associated with aggressive pathological characteristics in UC and independently predicted worse prognosis, suggesting it could play roles in clinical risk stratification and therapy decisions.https://www.mdpi.com/2227-9059/9/8/1054ROR2bladder cancerupper tract urothelial carcinomasurvivalprognosis
spellingShingle Cheng-Fa Yeh
Ti-Chun Chan
Hung-Lung Ke
Tzu-Ju Chen
Li-Ching Wu
Hsiang-Ying Lee
Yu-Ching Wei
Wen-Jeng Wu
Chien-Feng Li
Wei-Ming Li
Prognostic Significance of ROR2 Expression in Patients with Urothelial Carcinoma
Biomedicines
ROR2
bladder cancer
upper tract urothelial carcinoma
survival
prognosis
title Prognostic Significance of ROR2 Expression in Patients with Urothelial Carcinoma
title_full Prognostic Significance of ROR2 Expression in Patients with Urothelial Carcinoma
title_fullStr Prognostic Significance of ROR2 Expression in Patients with Urothelial Carcinoma
title_full_unstemmed Prognostic Significance of ROR2 Expression in Patients with Urothelial Carcinoma
title_short Prognostic Significance of ROR2 Expression in Patients with Urothelial Carcinoma
title_sort prognostic significance of ror2 expression in patients with urothelial carcinoma
topic ROR2
bladder cancer
upper tract urothelial carcinoma
survival
prognosis
url https://www.mdpi.com/2227-9059/9/8/1054
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