Proteogenomic Analysis Identifies Clinically Relevant Subgroups of Collecting Duct Carcinoma.

IF 10.7 1区综合性期刊 Q1 Multidisciplinary

Research Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI:10.34133/research.0859

Yuanyuan Qu, Xiaoru Pei, Jinwen Feng, Xin Yan, Linhui Zhang, Jun Wang, Xin Yao, Jiasheng Bian, Yu Gan, Hualei Gan, Xuewen Jiang, Ping Yang, Maoping Cai, Liqing Li, Xinqiang Wu, Weiwei Jing, Chao Zhang, Jianyuan Zhao, Hailiang Zhang, Guohai Shi, Xiang Zhou, Dingwei Ye, Chen Ding

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Abstract

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 UTP6 and HN1 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.

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蛋白质基因组学分析鉴定收集管癌临床相关亚群。

集管癌（CDC）是一种罕见但侵袭性的肾细胞癌（RCC），对其认识有限，系统治疗方案不明确。在此，我们对CDC肿瘤和正常邻近组织进行了全面的蛋白质基因组学分析，以阐明该疾病的生物学。CDC在肿瘤突变负担上具有较高的异质性，核糖体生物发生增强是CDC最显著的恶性特征，即使与其他常见肾癌相比也是如此。基因组数据显示，17q染色体上的UTP6和HN1扩增分别与核糖体生物发生激活和细胞迁移激活有关，与肿瘤的增殖和转移有关。基于蛋白质组学的分类鉴定出3个簇，其中，过表达核糖体生物发生信号（GP1）的肿瘤聚集为最具侵袭性的亚型，而能量代谢增加的肿瘤（GP3）对抗血管内皮生长因子药物表现出显著的敏感性。免疫分型揭示了CDC复杂的免疫格局。此外，增加的RPF2有助于核糖体的产生，被证实与恶性表型相关，靶向RPF2可以通过破坏核糖体的生物发生和干扰MDM2-p53的相互作用来发挥抗癌作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Research Multidisciplinary-Multidisciplinary

CiteScore

13.40

自引率

3.60%

发文量

审稿时长

14 weeks

期刊介绍： Research serves as a global platform for academic exchange, collaboration, and technological advancements. This journal welcomes high-quality research contributions from any domain, with open arms to authors from around the globe. Comprising fundamental research in the life and physical sciences, Research also highlights significant findings and issues in engineering and applied science. The journal proudly features original research articles, reviews, perspectives, and editorials, fostering a diverse and dynamic scholarly environment.