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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MDPI AG
2021-08-01
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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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