Proteogenomics of different urothelial bladder cancer stages reveals distinct molecular features for papillary cancer and carcinoma in situ

Zhenmei Yao, Ning Xu, Guoguo Shang, Haixing Wang, Hui Tao, Yunzhi Wang, Zhaoyu Qin, Subei Tan, Jinwen Feng, Jiajun Zhu, Fahan Ma, Sha Tian, Qiao Zhang, Yuanyuan Qu, Jun Hou (), Jianming Guo (), Jianyuan Zhao (), Yingyong Hou () and Chen Ding ()
Additional contact information
Zhenmei Yao: Fudan University
Ning Xu: Fudan University
Guoguo Shang: Fudan University
Haixing Wang: Fudan University
Hui Tao: Anhui Medical University
Yunzhi Wang: Fudan University
Zhaoyu Qin: Fudan University
Subei Tan: Fudan University
Jinwen Feng: Fudan University
Jiajun Zhu: Fudan University
Fahan Ma: Fudan University
Sha Tian: Fudan University
Qiao Zhang: Fudan University
Yuanyuan Qu: Fudan University, Shanghai Genitourinary Cancer Institute
Jun Hou: Fudan University
Jianming Guo: Fudan University
Jianyuan Zhao: Shanghai Jiao Tong University School of Medicine
Yingyong Hou: Fudan University
Chen Ding: Fudan University

Nature Communications, 2023, vol. 14, issue 1, 1-25

Abstract: Abstract The progression of urothelial bladder cancer (UC) is a complicated multi-step process. We perform a comprehensive multi-omics analysis of 448 samples from 190 UC patients, covering the whole spectrum of disease stages and grades. Proteogenomic integration analysis indicates the mutations of HRAS regulated mTOR signaling to form urothelial papilloma rather than papillary urothelial cancer (PUC). DNA damage is a key signaling pathway in the progression of carcinoma in situ (CIS) and related to APOBEC signature. Glucolipid metabolism increase and lower immune cell infiltration are associated with PUC compared to CIS. Proteomic analysis distinguishes the origins of invasive tumors (PUC-derived and CIS-derived), related to distinct clinical prognosis and molecular features. Additionally, loss of RBPMS, associated with CIS-derived tumors, is validated to increase the activity of AP-1 and promote metastasis. This study reveals the characteristics of two distinct branches (PUC and CIS) of UC progression and may eventually benefit clinical practice.

Date: 2023
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DOI: 10.1038/s41467-023-41139-3

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