干旱区生态环境知识资源中心(Arid): Ubiquitin Modification Patterns of Clear Cell Renal Cell Carcinoma and the Ubiquitin Score to Aid Immunotherapy and Targeted Therapy

Arid

DOI	10.3389/fcell.2021.659294
	Ubiquitin Modification Patterns of Clear Cell Renal Cell Carcinoma and the Ubiquitin Score to Aid Immunotherapy and Targeted Therapy
	Zhou, Peng; Lu, Yuchao; Xun, Yang; Xu, Jinzhou; Liu, Chenqian; Xia, Qidong; Lu, Junlin; Wang, Shaogang; Hu, Jia
通讯作者	Wang, SG ; Hu, J (corresponding author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Urol, Wuhan, Peoples R China.
来源期刊	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
ISSN	2296-634X
出版年	2021
卷号	9
英文摘要	Ubiquitin modification is the most common protein post-translational modification (PTM) process in organisms, and 1332 ubiquitin regulators have been identified in humans. Ubiquitin regulators, especially E3 ligases and deubiquitinases, are widely involved in immune processes. This study aims to explore the ubiquitin modification features of clear cell renal cell carcinoma (ccRCC) and to elucidate the role of such ubiquitin modifications in shaping anti-tumor immunity and individual benefits from immune checkpoint blockade (ICB). A comprehensive analysis was performed in the TCGA cohort (n = 530) and GEO cohort (n = 682). RNA sequencing data of 758 differentially expressed regulators, which was validated by the proteomics data, was used for k-means unsupervised consensus clustering and three ubiquitin patterns of ccRCC were identified. Then, we focused on the ubiquitin modification and tumor progression signatures, immune infiltration characteristics, and prognostic value. The three patterns with different ubiquitin modification signatures correspond to immune desert phenotype, immune resistance phenotype, and immune-inflammatory phenotype, respectively. To facilitate clinical application, we constructed a ubiquitin score to evaluate individual patients' ubiquitination outcome, and it was demonstrated to be an independent risk factor for overall survival (OS) in multivariate Cox analysis. It was found that the high score group was correlated to higher immune cells infiltrating level and PD-1/PD-L1/CTLA-4 expression. More importantly, we found that the high score group was predicted to be sensitive to anti-PD-1 treatment, while the low-score group showed lower predicted IC50 values in treatment with Pazopanib and Axitinib. In summary, this study elucidated the potential link between ubiquitin modification and immune infiltration landscape of ccRCC for the first time and provided a new assessment protocol for the precise selection of treatment strategies for patients with advanced ccRCC.
英文关键词	ubiquitin code unsupervised consensus clustering clear-cell renal-cell carcinoma immune signature immune checkpoint blockade targeted therapy
类型	Article
语种	英语
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000655186800001
WOS关键词	EXPRESSION ; CANCER ; PD-L1 ; DEGRADATION ; PROTEINS ; SUMO
WOS类目	Cell Biology ; Developmental Biology
WOS研究方向	Cell Biology ; Developmental Biology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/350269
作者单位	[Zhou, Peng; Lu, Yuchao; Xun, Yang; Xu, Jinzhou; Liu, Chenqian; Xia, Qidong; Lu, Junlin; Wang, Shaogang; Hu, Jia] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Urol, Wuhan, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Peng,Lu, Yuchao,Xun, Yang,et al. Ubiquitin Modification Patterns of Clear Cell Renal Cell Carcinoma and the Ubiquitin Score to Aid Immunotherapy and Targeted Therapy[J],2021,9.
APA	Zhou, Peng.,Lu, Yuchao.,Xun, Yang.,Xu, Jinzhou.,Liu, Chenqian.,...&Hu, Jia.(2021).Ubiquitin Modification Patterns of Clear Cell Renal Cell Carcinoma and the Ubiquitin Score to Aid Immunotherapy and Targeted Therapy.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,9.
MLA	Zhou, Peng,et al."Ubiquitin Modification Patterns of Clear Cell Renal Cell Carcinoma and the Ubiquitin Score to Aid Immunotherapy and Targeted Therapy".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 9(2021).