NTRK3 exhibits a pro-oncogenic function in upper tract urothelial carcinomas

Sep 21, 2026

Neurotrophic receptor tyrosine kinase 3 (NTRK3) performs multiple roles, functioning as an oncogene in some cancers and as a dependence receptor in others, yet its relevance in upper tract urothelial carcinoma (UTUC) remains insufficiently defined. This study assessed NTRK3 expression in 118 UTUC tissue samples, linked expression to patient outcomes using Kaplan–Meier and Cox regression, and validated findings in UTUC cell lines.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

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Abstract

Introduction

Methods

Results

Conclusions

DOI: 10.1002/kjm2.12824 O R IG INA L ARTI CLE NTRK3 exhibits a pro-oncogenic function in upper tract urothelial carcinomas Lee-Moay Lim 1,2,3 | Yi-Chen Lee 4,5 | Ting-Wei Lin 1 | Zi-Xuan Hong 1 | Wei-Chi Hsu 6 | Hung-Lung Ke 4,6,7,8 | Daw-Yang Hwang 9 | Wen-Yu Chung 10 | Wei-Ming Li 6,7,11 | Hui-Hui Lin 6,7 | Hung-Tien Kuo 2,3 | A-Mei Huang 1,4,12,13,14,15 1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 2Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 3School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 4Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 5Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 6Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 7Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 8Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 9National Institute of Cancer Research, National Health Research Institute, Tainan, Taiwan 10Department of Computer Science and Information Engineering, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan 11Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan 12Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 13Doctoral Degree Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan 14Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 15Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Correspondence A-Mei Huang, Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Road, Kaohsiung, 80708, Kaohsiung, Taiwan. Email: [amhuang@kmu.edu.tw](amhuang@kmu.edu.tw) Funding information Kaohsiung Medical University, Grant/Award Number: KMU-M112020 to A.M.H.; Kaohsiung Medical University Chung-Ho Memorial Hospital, Grant/Award Numbers: KMUH110-0R18, KMUH111-1R13 to L.M.L.; National Science and Technology Council, Grant/Award Numbers: MOST 109-2635-B- 037-009, MOST 110-2314-B-037-071, NSTC 111-2314-B-037-058 Abstract Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3 . Survival curves were generated using Kaplan–Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression-free survival, cancer-specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K-AKT-mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT-mTOR pathway. Furthermore, the This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. The Kaohsi

FAQs

What was the main objective of the study on NTRK3 in UTUC?

To determine whether NTRK3 expression is associated with outcomes in UTUC patients and to validate the findings using UTUC cell line experiments.

How many UTUC tissue samples were analyzed?

A total of 118 UTUC cancer tissue samples were examined for NTRK3 expression.

What relationship did the study find between NTRK3 expression and survival outcomes?

Higher NTRK3 expression correlated with worse progression-free survival, cancer-specific survival, and overall survival.

Sep 21, 2026

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