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A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population
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A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population
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Journal Article
A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population
2022
Overview
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.
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 82/58
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Cancer
/ Carcinoma, Renal Cell - pathology
/ China
/ Clear cell-type renal cell carcinoma
/ DNA
/ DNA-dependent protein kinase
/ Female
/ Genomics
/ Humanities and Social Sciences
/ Humans
/ Kidney Neoplasms - pathology
/ Kinases
/ Male
/ Mutation
/ Nicotinamide N-methyltransferase
/ Science
/ Tumors
