Plasma proteomic profiling discovers molecular features associated with upper tract urothelial carcinoma

Yuanyuan Qu; Zhenmei Yao; Ning Xu; Guohai Shi; Jiaqi Su; Shiqi Ye; Kun Chang; Kai Li; Yunzhi Wang; Subei Tan; Xiaoru Pei; Yijiao Chen; Zhaoyu Qin; Jinwen Feng; Jiacheng Lv; Jiajun Zhu; Fahan Ma; Shaoshuai Tang; Wenhao Xu; Xi Tian; Aihetaimujiang Anwaier; Sha Tian; Wenbo Xu; Xinqiang Wu; Shuxuan Zhu; Yu Zhu; Dalong Cao; Menghong Sun; Hualei Gan; Jianyuan Zhao; Hailiang Zhang; Dingwei Ye; Chen Ding

doi:10.1016/j.xcrm.2023.101166

Plasma proteomic profiling discovers molecular features associated with upper tract urothelial carcinoma

Cell Rep Med. 2023 Sep 19;4(9):101166. doi: 10.1016/j.xcrm.2023.101166. Epub 2023 Aug 25.

Authors

Yuanyuan Qu¹, Zhenmei Yao², Ning Xu², Guohai Shi¹, Jiaqi Su¹, Shiqi Ye¹, Kun Chang¹, Kai Li², Yunzhi Wang², Subei Tan², Xiaoru Pei², Yijiao Chen², Zhaoyu Qin², Jinwen Feng², Jiacheng Lv², Jiajun Zhu², Fahan Ma², Shaoshuai Tang², Wenhao Xu¹, Xi Tian¹, Aihetaimujiang Anwaier¹, Sha Tian², Wenbo Xu², Xinqiang Wu¹, Shuxuan Zhu¹, Yu Zhu¹, Dalong Cao¹, Menghong Sun³, Hualei Gan³, Jianyuan Zhao⁴, Hailiang Zhang⁵, Dingwei Ye⁶, Chen Ding⁷

Affiliations

¹ Department of Urology, Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University, Shanghai 200433, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Genitourinary Cancer Institute, Shanghai 200032, China.
² Department of Urology, Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University, Shanghai 200433, China.
³ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Genitourinary Cancer Institute, Shanghai 200032, China; Tissue Bank & Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
⁴ Institute for Development 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. Electronic address: zhaojy@fudan.edu.cn.
⁵ Department of Urology, Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University, Shanghai 200433, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Genitourinary Cancer Institute, Shanghai 200032, China. Electronic address: zhanghl918@163.com.
⁶ Department of Urology, Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University, Shanghai 200433, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Genitourinary Cancer Institute, Shanghai 200032, China. Electronic address: dwyeli@163.com.
⁷ Department of Urology, Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, and Human Phenome Institute, Fudan University, Shanghai 200433, China. Electronic address: chend@fudan.edu.cn.

Abstract

Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Limited data are available on potential non-invasive biomarkers for disease monitoring. Here, we investigate the proteomic profile of plasma in 362 UTUC patients and 239 healthy controls. We present an integrated tissue-plasma proteomic approach to infer the signature proteins for identifying patients with muscle-invasive UTUC. We discover a protein panel that reflects lymph node metastasis, which is of interest in identifying UTUC patients with high risk and poor prognosis. We also identify a ten-protein classifier and establish a progression clock predicting progression-free survival of UTUC patients. Finally, we further validate the signature proteins by parallel reaction monitoring assay in an independent cohort. Collectively, this study portrays the plasma proteomic landscape of a UTUC cohort and provides a valuable resource for further biological and diagnostic research in UTUC.

Keywords: DIA; mass spectrometry; plasma proteomics; prognosis; upper tract urothelial carcinoma.

Publication types

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

MeSH terms

Carcinoma, Transitional Cell* / diagnosis
Humans
Lymphatic Metastasis
Muscles
Proteomics
Urinary Bladder Neoplasms*