Journal Article

Integrated proteogenomic characterization of urothelial carcinoma of the bladder

Xu, Fujiang, Zhu, Jiajun, Zhang, Hailiang, Yao, Zhenmei, Zhao, Jianyuan, Ye, Dingwei, Liu, Yang, Hou, Jun, Tian, Sha, Zhang, Fan, Ding, Chen, Shang, Guoguo, Wang, Haixing, Xu, Ning, Qin, Zhaoyu, Hou, Yingyong, Qu, Yuanyuan, Guo, Jianming, Wang, Yunzhi, Feng, Jinwen

2022

Overview

Background Urothelial carcinoma (UC) is the most common pathological type of bladder cancer, a malignant tumor. However, an integrated multi-omics analysis of the Chinese UC patient cohort is lacking. Methods We performed an integrated multi-omics analysis, including whole-exome sequencing, RNA-seq, proteomic, and phosphoproteomic analysis of 116 Chinese UC patients, comprising 45 non-muscle-invasive bladder cancer patients (NMIBCs) and 71 muscle-invasive bladder cancer patients (MIBCs). Result Proteogenomic integration analysis indicated that SND1 and CDK5 amplifications on chromosome 7q were associated with the activation of STAT3, which was relevant to tumor proliferation. Chromosome 5p gain in NMIBC patients was a high-risk factor, through modulating actin cytoskeleton implicating in tumor cells invasion. Phosphoproteomic analysis of tumors and morphologically normal human urothelium produced UC-associated activated kinases, including CDK1 and PRKDC. Proteomic analysis identified three groups, U-I, U-II, and U-III, reflecting distinct clinical prognosis and molecular signatures. Immune subtypes of UC tumors revealed a complex immune landscape and suggested the amplification of TRAF2 related to the increased expression of PD-L1. Additionally, increased GARS, related to subtype U-II, was validated to promote pentose phosphate pathway by inhibiting activities of PGK1 and PKM2. Conclusions This study provides a valuable resource for researchers and clinicians to further identify molecular pathogenesis and therapeutic opportunities in urothelial carcinoma of the bladder.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Actin / Analysis / Biomarkers, Tumor - genetics / Bladder cancer / Cancer / Cancer Research / Cancer therapies / Carcinoma / Carcinoma, Transitional Cell - genetics / Carcinoma, Transitional Cell - pathology / Chromosome 5 / Chromosome 7 / Cytoskeleton / Development and progression / Endonucleases / FDA approval / Genetic aspects / Genome / Genomics / Hematology / Humans / Instrument industry / Invasiveness / Medical prognosis / Medical research / Medicine / Medicine & Public Health / Muscle proteins / Mutation / Oncology / Patients / PD-L1 protein / Pentose phosphate pathway / Peptides / Phosphates / Phosphoproteomics / Proteins / Proteogenomics / Proteomic subtype / Proteomics / Risk factors / RNA / RNA-seq / Scientific equipment and supplies industry / Stat3 protein / TRAF2 protein / Tumor cells / Tumors / Urinary Bladder - chemistry / Urinary Bladder - metabolism / Urinary Bladder - pathology / Urinary Bladder Neoplasms - genetics / Urinary Bladder Neoplasms - pathology / Urothelial carcinoma / Urothelial carcinoma of the bladder / Urothelium