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

Yuanyuan Qu, Jinwen Feng, Xiaohui Wu, Lin Bai, Wenhao Xu, Lingli Zhu, Yang Liu, Fujiang Xu, Xuan Zhang, Guojian Yang, Jiacheng Lv, Xiuping Chen, Guo-Hai Shi, Hong-Kai Wang, Da-Long Cao, Hang Xiang, Lingling Li, Subei Tan, Hua-Lei Gan, Meng-Hong Sun, Jiange Qiu, Hailiang Zhang (), Jian-Yuan Zhao (), Dingwei Ye () and Chen Ding ()
Additional contact information
Yuanyuan Qu: Fudan University
Jinwen Feng: Fudan University
Xiaohui Wu: Fudan University
Lin Bai: Fudan University
Wenhao Xu: Fudan University
Lingli Zhu: Fudan University
Yang Liu: Fudan University
Fujiang Xu: Fudan University
Xuan Zhang: Fudan University
Guojian Yang: Fudan University
Jiacheng Lv: Fudan University
Xiuping Chen: Fudan University
Guo-Hai Shi: Fudan University
Hong-Kai Wang: Fudan University
Da-Long Cao: Fudan University
Hang Xiang: Fudan University
Lingling Li: Fudan University
Subei Tan: Fudan University
Hua-Lei Gan: Shanghai Medical College
Meng-Hong Sun: Shanghai Medical College
Jiange Qiu: Zhengzhou University
Hailiang Zhang: Fudan University
Jian-Yuan Zhao: Fudan University
Dingwei Ye: Fudan University
Chen Ding: Fudan University

Nature Communications, 2022, vol. 13, issue 1, 1-21

Abstract: Abstract 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29577-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29577-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-29577-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().