Dataset Information

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

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.

SUBMITTER: Yao Z

PROVIDER: S-EPMC10499981 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Yao Zhenmei Z Xu Ning N Shang Guoguo G Wang Haixing H Tao Hui H Wang Yunzhi Y Qin Zhaoyu Z Tan Subei S Feng Jinwen J Zhu Jiajun J Ma Fahan F Tian Sha S Zhang Qiao Q Qu Yuanyuan Y Hou Jun J Guo Jianming J Zhao Jianyuan J Hou Yingyong Y Ding Chen C

Nature communications 20230913 1

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 APO ...[more]

PMID: 37704624

Similar Datasets

Project description:BackgroundThe first global lipidomic profiles associated with urothelial cancer of the bladder (UCB) and its clinical stages associated with progression were identified.ObjectiveTo identify lipidomic signatures associated with survival and different clinical stages of UCB.Design, setting, and participantsPathologically confirmed 165 bladder-derived tissues (126 UCB, 39 benign adjacent or normal bladder tissues). UCB tissues included Ta (n=16), T1 (n=30), T2 (n=43), T3 (n=27), and T4 (n=9); lymphovascular invasion (LVI) positive (n=52) and negative (n=69); and lymph node status N0 (n=28), N1 (n=11), N2 (n=9), N3 (n=3), and Nx (n=75).Results and limitationsUCB tissues have higher levels of phospholipids and fatty acids, and reduced levels of triglycerides compared with benign tissues. A total of 59 genes associated with altered lipids in UCB strongly correlate with patient survival in an UCB public dataset. Within UCB, there was a progressive decrease in the levels of phosphatidylserine (PS), phosphatidylethanolamines (PEs), and phosphocholines, whereas an increase in the levels of diacylglycerols (DGs) with tumor stage. Transcript and protein expression of phosphatidylserine synthase 1, which converts DGs to PSs, decreased progressively with tumor stage. Levels of DGs and lyso-PEs were significantly elevated in tumors with LVI and lymph node involvement, respectively. Lack of carcinoma in situ and treatment information is the limitation of our study.ConclusionsTo date, this is the first study describing the global lipidomic profiles associated with UCB and identifies lipids associated with tumor stages, LVI, and lymph node status. Our data suggest that triglycerides serve as the primary energy source in UCB, while phospholipid alterations could affect membrane structure and/or signaling associated with tumor progression.Patient summaryLipidomic alterations identified in this study set the stage for characterization of pathways associated with these altered lipids that, in turn, could inform the development of first-of-its-kind lipid-based noninvasive biomarkers and novel therapeutic targets for aggressive urothelial cancer of the bladder.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets