Integrated proteogenomic characterization of urothelial carcinoma of the bladder.

Abstract

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.

• Authors: Ning Xu, Zhenmei Yao, Guoguo Shang, Dingwei Ye, Haixing Wang, Hailiang Zhang, Yuanyuan Qu, Fujiang Xu, Yunzhi Wang, Zhaoyu Qin, Jiajun Zhu, Fan Zhang, Jinwen Feng, Sha Tian, Yang Liu, Jianyuan Zhao, Jun Hou, Jianming Guo, Yingyong Hou, Chen Ding
• Journal: Journal of hematology & oncology (J Hematol Oncol) Vol. 15 Issue 1 Pg. 76 (06 03 2022) ISSN: 1756-8722 [Electronic] England
• PMID: 35659036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Biomarkers, Tumor
• Endonucleases
• SND1 protein, human

Topics

• Biomarkers, Tumor (genetics)
• Carcinoma, Transitional Cell (genetics, pathology)
• Endonucleases
• Humans
• Proteogenomics
• Proteomics
• Urinary Bladder (chemistry, metabolism, pathology)
• Urinary Bladder Neoplasms (genetics, pathology)