Proteogenomics of Different Urothelial Bladder Cancer Stages Reveals Distinct Molecular Features for Papillary Cancer and Carcinoma in Situ

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Sep 13

PMID 37704624

Authors

Zhenmei Yao

Ning Xu

Guoguo Shang

Haixing Wang

Hui Tao

Yunzhi Wang

Zhaoyu Qin

Subei Tan

Jinwen Feng

Jiajun Zhu

Fahan Ma

Sha Tian

Qiao Zhang

Yuanyuan Qu

Jun Hou

Jianming Guo

Jianyuan Zhao

Yingyong Hou

Chen Ding

Affiliations

Soon will be listed here.

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.

Citing Articles

Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy.

Contreras-Sanz A, Negri G, Reike M, Oo H, Scurll J, Spencer S Nat Commun. 2025; 16(1):1240.

PMID: 39890781 PMC: 11785721. DOI: 10.1038/s41467-024-55665-1.

Loss of YTHDC1 mA reading function promotes invasiveness in urothelial carcinoma of the bladder.

Xu J, Koch J, Schmidt C, Nientiedt M, Neuberger M, Erben P Exp Mol Med. 2024; 57(1):118-130.

PMID: 39741187 PMC: 11799412. DOI: 10.1038/s12276-024-01377-x.

Tumor-Intrinsic Kinome Landscape of Pancreatic Cancer Reveals New Therapeutic Approaches.

Xu Y, Peng X, East M, McCabe I, Stroman G, Jenner M Cancer Discov. 2024; 15(2):346-362.

PMID: 39632628 PMC: 11805639. DOI: 10.1158/2159-8290.CD-23-1480.

What is a Bladder Cancer Molecular Subtype? - Counterpoint.

Radvanyi F, Real F, McConkey D Bladder Cancer. 2024; 9(4):299-304.

PMID: 38994248 PMC: 11165934. DOI: 10.3233/BLC-230059.

Comprehensive multi-omics analysis of breast cancer reveals distinct long-term prognostic subtypes.

Sharma A, Debik J, Naume B, Ohnstad H, Bathen T, Giskeodegard G Oncogenesis. 2024; 13(1):22.

PMID: 38871719 PMC: 11176181. DOI: 10.1038/s41389-024-00521-6.

References

Bakiri L, Matsuo K, Wisniewska M, Wagner E, Yaniv M . Promoter specificity and biological activity of tethered AP-1 dimers. Mol Cell Biol. 2002; 22(13):4952-64. PMC: 133900. DOI: 10.1128/MCB.22.13.4952-4964.2002. View

Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F . Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. Eur Urol. 2016; 71(1):96-108. DOI: 10.1016/j.eururo.2016.06.010. View

Chen S, Li F, Xu D, Hou K, Fang W, Li Y . The Function of RAS Mutation in Cancer and Advances in its Drug Research. Curr Pharm Des. 2019; 25(10):1105-1114. DOI: 10.2174/1381612825666190506122228. View

Lindskrog S, Prip F, Lamy P, Taber A, Groeneveld C, Birkenkamp-Demtroder K . An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer. Nat Commun. 2021; 12(1):2301. PMC: 8052448. DOI: 10.1038/s41467-021-22465-w. View

Chen Y, Chang L . NFκB- and AP-1-mediated DNA looping regulates matrix metalloproteinase-9 transcription in TNF-α-treated human leukemia U937 cells. Biochim Biophys Acta. 2015; 1849(10):1248-59. DOI: 10.1016/j.bbagrm.2015.07.016. View

Middlebrooks C, Rouf Banday A, Matsuda K, Udquim K, Onabajo O, Paquin A . Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors. Nat Genet. 2016; 48(11):1330-1338. PMC: 6583788. DOI: 10.1038/ng.3670. View

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

Czerniak B, Dinney C, McConkey D . Origins of Bladder Cancer. Annu Rev Pathol. 2016; 11:149-74. DOI: 10.1146/annurev-pathol-012513-104703. View

Sies H, Jones D . Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020; 21(7):363-383. DOI: 10.1038/s41580-020-0230-3. View

10.

Kirkali Z, Chan T, Manoharan M, Algaba F, Busch C, Cheng L . Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology. 2006; 66(6 Suppl 1):4-34. DOI: 10.1016/j.urology.2005.07.062. View

11.

Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S . A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature. 2008; 456(7219):269-73. PMC: 2597669. DOI: 10.1038/nature07349. View

12.

Chen Y, Zander R, Khatun A, Schauder D, Cui W . Transcriptional and Epigenetic Regulation of Effector and Memory CD8 T Cell Differentiation. Front Immunol. 2018; 9:2826. PMC: 6292868. DOI: 10.3389/fimmu.2018.02826. View

13.

Krug K, Mertins P, Zhang B, Hornbeck P, Raju R, Ahmad R . A Curated Resource for Phosphosite-specific Signature Analysis. Mol Cell Proteomics. 2018; 18(3):576-593. PMC: 6398202. DOI: 10.1074/mcp.TIR118.000943. View

14.

Abecasis G, Auton A, Brooks L, DePristo M, Durbin R, Handsaker R . An integrated map of genetic variation from 1,092 human genomes. Nature. 2012; 491(7422):56-65. PMC: 3498066. DOI: 10.1038/nature11632. View

15.

Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat E . EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. 2016; 71(3):447-461. DOI: 10.1016/j.eururo.2016.05.041. View

16.

Croft D, Mundo A, Haw R, Milacic M, Weiser J, Wu G . The Reactome pathway knowledgebase. Nucleic Acids Res. 2013; 42(Database issue):D472-7. PMC: 3965010. DOI: 10.1093/nar/gkt1102. View

17.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

18.

Matsuoka S, Ballif B, Smogorzewska A, McDonald 3rd E, Hurov K, Luo J . ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007; 316(5828):1160-6. DOI: 10.1126/science.1140321. View

19.

Sung M, Eble J, Wang M, Tan P, Lopez-Beltran A, Cheng L . Inverted papilloma of the urinary bladder: a molecular genetic appraisal. Mod Pathol. 2006; 19(10):1289-94. DOI: 10.1038/modpathol.3800667. View

20.

Ku X, Wang J, Li H, Meng C, Yu F, Yu W . Proteomic Portrait of Human Lymphoma Reveals Protein Molecular Fingerprint of Disease Specific Subtypes and Progression. Phenomics. 2023; 3(2):148-166. PMC: 10110798. DOI: 10.1007/s43657-022-00075-w. View