Proteogenomics of different urothelial bladder cancer stages reveals distinct molecular features for papillary cancer and carcinoma in situ.
Zhenmei YaoNing XuGuoguo ShangHaixing WangHui TaoYunzhi WangZhaoyu QinSubei TanJinwen FengJiajun ZhuFahan MaSha TianQiao ZhangYuanyuan QuJun HouJianming GuoJian-Yuan ZhaoYing-Yong HouChen DingPublished in: Nature communications (2023)
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.
Keyphrases
- high grade
- urinary tract
- dna damage
- papillary thyroid
- signaling pathway
- end stage renal disease
- clinical practice
- squamous cell
- transcription factor
- ejection fraction
- newly diagnosed
- oxidative stress
- chronic kidney disease
- prognostic factors
- epithelial mesenchymal transition
- cell proliferation
- lymph node metastasis
- single molecule
- peritoneal dialysis
- squamous cell carcinoma
- patient reported outcomes
- childhood cancer
- clear cell
- endoplasmic reticulum stress
- muscle invasive bladder cancer