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; Chen Ding

doi:10.1038/s41467-023-41139-3

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

Nat Commun. 2023 Sep 13;14(1):5670. doi: 10.1038/s41467-023-41139-3.

Authors

Zhenmei Yao^#¹, Ning Xu^#¹, Guoguo Shang^#¹, Haixing Wang^#¹, Hui Tao^#², Yunzhi Wang¹, Zhaoyu Qin¹, Subei Tan¹, Jinwen Feng¹, Jiajun Zhu¹, Fahan Ma¹, Sha Tian¹, Qiao Zhang¹, Yuanyuan Qu³, Jun Hou⁴, Jianming Guo⁵, Jianyuan Zhao^{6

7}, Yingyong Hou⁸, Chen Ding⁹

Affiliations

¹ 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, Fudan University, Shanghai, 200433, China.
² Department of Cardiothoracic Surgery, Second Hospital of Anhui Medical University, and Cardiovascular Research Center, Anhui Medical University, Hefei, 230601, China.
³ Department of Urology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Genitourinary Cancer Institute, Shanghai, 200032, China.
⁴ 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, Fudan University, Shanghai, 200433, China. Hou.Jun@zs-hospital.sh.cn.
⁵ 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, Fudan University, Shanghai, 200433, China. guo.jianmin@zs-hospital.sh.cn.
⁶ Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. zhaojy@fudan.edu.cn.
⁷ School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China. zhaojy@fudan.edu.cn.
⁸ 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, Fudan University, Shanghai, 200433, China. hou.yingyong@zs-hospital.sh.cn.
⁹ 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, Fudan University, Shanghai, 200433, China. chend@fudan.edu.cn.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma in Situ*
Carcinoma, Papillary* / genetics
Carcinoma, Transitional Cell*
Humans
Proteogenomics*
Proteomics
Urinary Bladder Neoplasms* / genetics