A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population

被引：9

作者：

Qu, Yuanyuan ^{[1
,2
,3
]}

Feng, Jinwen ^{[1
,2
]}

Wu, Xiaohui ^{[1
,2
]}

Bai, Lin ^{[1
,2
]}

Xu, Wenhao ^{[1
,2
,3
]}

Zhu, Lingli ^{[1
,2
]}

Liu, Yang ^{[1
,2
]}

Xu, Fujiang ^{[1
,2
]}

Zhang, Xuan ^{[1
,2
]}

Yang, Guojian ^{[1
,2
]}

Lv, Jiacheng ^{[1
,2
]}

Chen, Xiuping ^{[1
,2
]}

Shi, Guo-Hai ^{[1
,2
,3
]}

Wang, Hong-Kai ^{[1
,2
,3
]}

Cao, Da-Long ^{[1
,2
,3
]}

Xiang, Hang ^{[1
,2
]}

Li, Lingling ^{[1
,2
]}

Tan, Subei ^{[1
,2
]}

Gan, Hua-Lei ^{[3
,4
,5
]}

Sun, Meng-Hong ^{[3
,4
,5
]}

Qiu, Jiange ^{[6
]}

Zhang, Hailiang ^{[1
,2
,3
]}

Zhao, Jian-Yuan ^{[1
,2
,7
]}

Ye, Dingwei ^{[1
,2
,3
]}

Ding, Chen ^{[1
,2
]}

机构：

[1] Fudan Univ, Shanghai Canc Ctr,Inst Biomed Sci, Collaborat Innovat Ctr Genet & Dev, Sch Life Sci,Dept Urol,State Key Lab Genet Engn, Shanghai, Peoples R China

[2] Fudan Univ, Human Phenome Inst, Shanghai, Peoples R China

[3] Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China

[4] Fudan Univ, Tissue Bank, Shanghai Canc Ctr, Shanghai, Peoples R China

[5] Fudan Univ, Dept Pathol, Shanghai Canc Ctr, Shanghai, Peoples R China

[6] Zhengzhou Univ, Acad Med Sci, Cell Signaling & Prote Res Ctr, Zhengzhou, Peoples R China

[7] Shanghai Jiao Tong Univ, Xinhua Hosp, Inst Dev & Regenerat Cardiovasc Med,Sch Med, MOE Shanghai Key Lab Childrens Environm Hlth, Shanghai, Peoples R China

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

基金：

上海市自然科学基金; 中国博士后科学基金; 国家重点研发计划; 中国国家自然科学基金;

关键词：

NICOTINAMIDE N-METHYLTRANSFERASE; SOMATIC MUTATIONS; CLASS DISCOVERY; CANCER; EXPRESSION; GENE; BIOMARKER; SURVIVAL; REVEALS; TOOL;

D O I：

10.1038/s41467-022-29577-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Clear cell renal cell carcinoma is an aggressive form of renal cancer, with differences in genomic mutations reported between Western and Eastern populations. In this study, the authors have compiled proteogenomic analysis of Chinese ccRCC to reveal genomic alterations and dysregulation of immune and metabolic responses. Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of renal cancer. Here we conduct a comprehensive proteogenomic analysis of 232 tumor and adjacent non-tumor tissue pairs from Chinese ccRCC patients. By comparing with tumor adjacent tissues, we find that ccRCC shows extensive metabolic dysregulation and an enhanced immune response. Molecular subtyping classifies ccRCC tumors into three subtypes (GP1-3), among which the most aggressive GP1 exhibits the strongest immune phenotype, increased metastasis, and metabolic imbalance, linking the multi-omics-derived phenotypes to clinical outcomes of ccRCC. Nicotinamide N-methyltransferase (NNMT), a one-carbon metabolic enzyme, is identified as a potential marker of ccRCC and a drug target for GP1. We demonstrate that NNMT induces DNA-dependent protein kinase catalytic subunit (DNA-PKcs) homocysteinylation, increases DNA repair, and promotes ccRCC tumor growth. This study provides insights into the biological underpinnings and prognosis assessment of ccRCC, revealing targetable metabolic vulnerabilities.

引用

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