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

Nature Communications (Sep 2023)

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

Affiliations

Zhenmei Yao: 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
Ning Xu: 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
Guoguo Shang: 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
Haixing Wang: 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
Hui Tao: Department of Cardiothoracic Surgery, Second Hospital of Anhui Medical University, and Cardiovascular Research Center, Anhui Medical University
Yunzhi Wang: 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
Zhaoyu Qin: 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
Subei Tan: 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
Jinwen Feng: 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
Jiajun Zhu: 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
Fahan Ma: 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
Sha Tian: 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
Qiao Zhang: 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
Yuanyuan Qu: Department of Urology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Genitourinary Cancer Institute
Jun Hou: 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
Jianming Guo: 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
Jianyuan Zhao: 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
Yingyong Hou: 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
Chen Ding: 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

DOI: https://doi.org/10.1038/s41467-023-41139-3
Journal volume & issue: Vol. 14, no. 1
pp. 1 – 25

Abstract

Read online

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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

About the journal