Proteogenomics of urothelial bladder cancer progression reveals the distinguished molecular features of different pathological subtypes

ABSTRACT: We reported a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 448 trace-tumor-samples from 190 urothelial bladder neoplasm patients, covering the whole spectrum of disease stages and grades. DNA damage was a key signaling pathway in the progression of carcinoma in situ (CIS) and related to APOBEC signature. Proteogenomic integration analysis indicated the mutation of HRAS regulated mTOR signaling to form urothelial papilloma rather than papillary urothelial cancer (PUC). Glucolipid metabolism increase and lower immune cell infiltration were significantly associated with PUC compared to CIS. Proteomic analysis distinguished 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, was validated to increase the activity of SMAD-bound JUN and promote metastasis.

ORGANISM(S): Homo Sapiens

SUBMITTER: Chen Ding  

PROVIDER: PXD043775 | iProX | Wed Aug 02 00:00:00 BST 2023

REPOSITORIES: iProX