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.

Urothelial bladder cancer (UC) progression occurs as a multi-step process that leads to different kinds of lesions and subtypes. Here, the authors characterise benign and invasive lesions that occur during UC progression using proteogenomics in patient samples and show critical molecular pathways and prognostic associations.

Details

Title
Proteogenomics of different urothelial bladder cancer stages reveals distinct molecular features for papillary cancer and carcinoma in situ
Author
Yao, Zhenmei 1 ; Xu, Ning 1 ; Shang, Guoguo 1 ; Wang, Haixing 1 ; Tao, Hui 2 ; Wang, Yunzhi 1   VIAFID ORCID Logo  ; Qin, Zhaoyu 1   VIAFID ORCID Logo  ; Tan, Subei 1   VIAFID ORCID Logo  ; Feng, Jinwen 1   VIAFID ORCID Logo  ; Zhu, Jiajun 1 ; Ma, Fahan 1   VIAFID ORCID Logo  ; Tian, Sha 1   VIAFID ORCID Logo  ; Zhang, Qiao 1 ; Qu, Yuanyuan 3 ; Hou, Jun 1 ; Guo, Jianming 1 ; Zhao, Jianyuan 4   VIAFID ORCID Logo  ; Hou, Yingyong 1   VIAFID ORCID Logo  ; Ding, Chen 1   VIAFID ORCID Logo 

1  Fudan University, State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Department of Pathology, Zhongshan Hospital, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
2  Anhui Medical University, Department of Cardiothoracic Surgery, Second Hospital of Anhui Medical University, and Cardiovascular Research Center, Hefei, China (GRID:grid.186775.a) (ISNI:0000 0000 9490 772X) 
3  Fudan University, Shanghai Genitourinary Cancer Institute, Department of Urology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
4  Shanghai Jiao Tong University School of Medicine, Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293); Zhengzhou University, School of Basic Medical Sciences, Zhengzhou, China (GRID:grid.207374.5) (ISNI:0000 0001 2189 3846) 
Pages
5670
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-023-41139-3
ProQuest document ID
2864389784
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.