Proteogenomic Analysis Identifies Clinically Relevant Subgroups of Collecting Duct Carcinoma
Collecting duct carcinoma (CDC) is a rare but aggressive form of renal cell carcinoma (RCC) that has limited understanding and an undefined systemic therapeutic regimen. Herein, we conducted a comprehensive proteogenomic analysis of CDC tumors and normal adjacent tissues to elucidate the biology of the disease. CDC exhibited high heterogeneity in tumor mutational burden, and enhanced ribosome biogenesis was the most striking malignant feature of CDC, even compared with other common kidney carcinomas. Genomic data indicated that <i>UTP6</i> and <i>HN1</i> amplification on chromosome 17q were associated with the activations of ribosome biogenesis and cell migration, respectively, which were relevant to tumor proliferation and metastasis. Proteomic-based classification identified 3 clusters, among which, tumors overexpressing ribosome biogenesis signaling (GP1) clustered into the most aggressive subtype, while tumors with increased energy metabolism (GP3) exhibited significant sensitivity to anti-vascular endothelial growth factor agents. Immune subtyping revealed a complex immune landscape of CDC. Additionally, increased RPF2, contributing to ribosome production, was validated to be associated with malignant phenotypes, and targeting RPF2 could exert an anti-oncogenic role by disrupting ribosome biogenesis and perturbing the MDM2-p53 interaction.
Authors
- Xiang Zhou (ORCID: https://orcid.org/0000-0003-3885-0919)
- Jinwen Feng (ORCID: https://orcid.org/0000-0003-1683-4280)
- Xin Yan (ORCID: https://orcid.org/0000-0003-0016-1632)
- Jiasheng Bian
- Xiaoru Pei
- Jun Wang (ORCID: https://orcid.org/0000-0001-7524-6783)
- Chao Zhang (ORCID: https://orcid.org/0000-0001-7096-8488)
- Wei Jing (ORCID: https://orcid.org/0000-0002-0573-2783)
- Chen Ding (ORCID: https://orcid.org/0000-0001-8673-3464)
- Jian‐Yuan Zhao (ORCID: https://orcid.org/0000-0001-9861-0330)
- Ping Yang (ORCID: https://orcid.org/0000-0002-9756-5635)
- Xuewen Jiang
- Xinqiang Wu (ORCID: https://orcid.org/0000-0002-6238-9993)
- Yuanyuan Qu (ORCID: https://orcid.org/0009-0006-5266-6228)
- Dingwei Ye (ORCID: https://orcid.org/0000-0003-4974-3780)
- Liqing Li (ORCID: https://orcid.org/0000-0002-0196-7710)
- Xin Yao (ORCID: https://orcid.org/0000-0002-1301-3631)
- Guo-Hai Shi
- Yu Gan
- Linhui Zhang (ORCID: https://orcid.org/0000-0002-4672-8350)
- Hualei Gan
- Maoping Cai (ORCID: https://orcid.org/0009-0009-2242-2582)
- Hai‐Liang Zhang
Institutions
- Xinjiang Medical University (CN)
- Sun Yat-sen University (CN)
- Fudan University (CN)
- XinHua Hospital (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Fudan University Shanghai Cancer Center (CN)
- Tumor Hospital of Xinjiang Medical University (CN)
- Huzhou Central Hospital (CN)
- Sun Yat-sen University Cancer Center (CN)
- Qilu Hospital of Shandong University (CN)
- Shandong First Medical University (CN)
Publication Details
- Journal
- Research
- Published
- 2025-01-01
- DOI
- https://doi.org/10.34133/research.0859
- Citations
- 1
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.94