Research Paper Volume 13, Issue 7 pp 10450—10467
RIPK2 is an unfavorable prognosis marker and a potential therapeutic target in human kidney renal clear cell carcinoma
- 1 Urology Department, First Hospital of Shanxi Medical University, First Clinical Collage of Shanxi Medical University, Shanxi Medical University, Taiyuan 030001, China
- 2 Department of Nephrology, Beijing-Chaoyang Hospital, Beijing 100020, China
- 3 Office of Academic Research, Beijing-Chaoyang Hospital, Beijing 100020, China
- 4 Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China
- 5 Department of Medicine, Shenzhen University, Guangdong 518061, China
- 6 Torch High Technology Industry Development Center, Ministry of Science and Technology, Beijing 100045, China
- 7 Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China
Received: March 20, 2020 Accepted: February 25, 2021 Published: March 31, 2021
https://doi.org/10.18632/aging.202808How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Receptor Interacting Serine/Threonine Kinase 2 (RIPK2) is located on chromosome 8q21 and encodes a protein containing a C-terminal caspase activation and recruitment domain (CARD), which is a component of signaling complexes in both the innate and adaptive immune pathways. To estimate the value of RIPK2 in evaluating the prognosis and guiding the targeted therapy for patients with kidney renal clear cell carcinoma (KIRC), we analyzed total 526 KIRC samples from The Cancer Genome Atlas (TCGA) database. Our result showed that RIPK2 was upregulated in KIRC tumor samples compared with normal samples. Cox regression was performed to calculate the hazard ratio of RIPK2 expression as an unfavorable prognosis feature for overall survival. Moreover, RIPK2 expression was positively correlated to the high-risk clinical stage, and metastasis features. The upregulation of RIPK2 was strongly correlated with various immune signaling pathway dysregulations as well as immune phenotypes changes in KIRC patient’s cohort. In addition, inhibition of RIPK2 activity by either shRNA-mediated knockdown or inhibitor significantly reduced kidney cancer cell viability, trans-migration in vitro, and impaired tumor growth in vivo. In conclusion, elevated RIPK2 expression indicates a worse prognosis for KIRC patients and could serve as a potential prognostic biomarker and therapeutic target in kidney cancer.
Abbreviations
TCGA: the cancer genome atlas; KIRC: kidney renal clear cell carcinoma; GSEA: gene-set enrichment analysis.