Proteogenomic characterization of MiT family translocation renal cell carcinoma

• DOI: 10.1038/s41467-022-34460-w
• Publication Date: 2022-12-05T17:03:08Z
• Authors: Yuanyuan Qu; Xiaohui Wu; Aihetaimujiang An...; Jinwen Feng; Wenhao Xu; Xiaoru Pei; Yu Zhu; Yang Liu; Lin Bai; Guojian Yang; Xi Tian; Jiaqi Su; Guo-Hai Shi; Da-Long Cao; Fujiang Xu; Yue Wang; Hua-Lei Gan; Shujuan Ni; Meng-Hong Sun; Jian-Yuan Zhao; Hailiang Zhang; Dingwei Ye; Chen Ding
• Keywords: Proteomics; 0301 basic medicine; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Science; Q; Article; Kidney Neoplasms; Translocation, Genetic; 3. Good health; 03 medical and health sciences; Humans; Microphthalmos; Carcinoma, Renal Cell; Proteogenomics; Transcription Factors

AbstractMicrophthalmia transcription factor (MiT) family translocation renal cell carcinoma (tRCC) is a rare type of kidney cancer, which is not well characterized. Here we show the comprehensive proteogenomic analysis of tRCC tumors and normal adjacent tissues to elucidate the molecular landscape of this disease. Our study reveals that defective DNA repair plays an important role in tRCC carcinogenesis and progression. Metabolic processes are markedly dysregulated at both the mRNA and protein levels. Proteomic and phosphoproteome data identify mTOR signaling pathway as a potential therapeutic target. Moreover, molecular subtyping and immune infiltration analysis characterize the inter-tumoral heterogeneity of tRCC. Multi-omic integration reveals the dysregulation of cellular processes affected by genomic alterations, including oxidative phosphorylation, autophagy, transcription factor activity, and proteasome function. This study represents a comprehensive proteogenomic analysis of tRCC, providing valuable insights into its biological mechanisms, disease diagnosis, and prognostication.