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Proteogenomic Analysis Identifies Clinically Relevant Subgroups of Collecting Duct Carcinoma
Yuanyuan Qu1,2, Xiaoru Pei1, Jinwen Feng1
1Department of Urology, Fudan University Shanghai Cancer Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200433, China.
Research (Washington, D.C.)
|September 8, 2025
Summary
Collecting duct carcinoma (CDC) is a rare kidney cancer. Proteogenomic analysis reveals enhanced ribosome biogenesis as a key driver of CDC aggressiveness and metastasis, suggesting new therapeutic targets.
Area of Science:
- Oncology
- Genomics
- Proteomics
Background:
- Collecting duct carcinoma (CDC) is a rare and aggressive subtype of renal cell carcinoma (RCC).
- Limited understanding exists regarding its underlying biology and effective systemic treatments.
- A comprehensive proteogenomic approach is needed to elucidate CDC pathogenesis.
Purpose of the Study:
- To conduct a comprehensive proteogenomic analysis of CDC tumors and adjacent normal tissues.
- To identify key molecular features driving CDC aggressiveness and potential therapeutic vulnerabilities.
- To understand the complex immune landscape within CDC tumors.
Main Methods:
- Proteogenomic analysis integrating genomic and proteomic data from CDC tumors and normal tissues.
- Assessment of tumor mutational burden and chromosomal amplifications (e.g., 17q).
- Proteomic-based and immune subtyping of tumors.
Main Results:
- CDC exhibits high tumor mutational burden heterogeneity.
- Enhanced ribosome biogenesis is a prominent malignant feature in CDC, surpassing other kidney carcinomas.
- UTP6 and HN1 amplifications correlate with ribosome biogenesis and cell migration, respectively.
- Proteomic subtypes revealed aggressive (GP1, ribosome biogenesis) and potentially sensitive (GP3, energy metabolism to anti-VEGF) groups.
- RPF2 overexpression is linked to malignant phenotypes and may be a therapeutic target.
Conclusions:
- Enhanced ribosome biogenesis is a critical driver of collecting duct carcinoma aggressiveness and metastasis.
- Specific genomic alterations (UTP6, HN1) and protein expression (RPF2) are associated with tumor progression.
- Proteomic and immune profiling reveals distinct subtypes and potential therapeutic strategies, including targeting ribosome biogenesis and anti-VEGF therapy.
