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Methods: Whole-exome and RNA sequencing were performed in total on 96 primary NMIBCs including 22 G1 pTa, 14 G3 pTa and 53 G3 pT1s, with both exome and RNA sequencing data generated from 75 of these individual samples. Associations between genomic alterations, expression profiles and progression-free survival (PFS) were investigated.
Results: NMIBCs clustered into 3 expression subtypes with different somatic alteration characteristics. Amplifications of ARNT and ERBB2 were significant indicators of worse PFS across all NMIBCs. High APOBEC mutagenesis and high tumour mutation burden were both potential indicators of better PFS in G3pT1 NMIBCs. The expression of individual genes was not prognostic in BCG-treated G3pT1 NMIBCs; however, downregulated interferon-alpha and gamma response pathways were significantly associated with worse PFS (adjusted p-value < 0.005).
Conclusions: Multi-omic data may facilitate better prognostication and selection of therapeutic interventions in patients with G3pT1 NMIBC. These findings demonstrate the potential for improving the management of high-risk NMIBC patients and warrant further prospective validation.
Bibliographical noteFunding Information:
ND James has contributed to the advisory boards for Merck USA and Pierre Fabre. RT Bryan has contributed to the advisory boards for Olympus Medical Systems, Janssen and Nonacus Limited and has undertaken research funded by UroGen Pharma, QED Therapeutics and Janssen. DG Ward has contributed to the advisory boards for Nonacus Limited. The remaining authors declare that they have no competing interests.
The Bladder Cancer Prognosis Programme (BCPP) was funded by Cancer Research UK (C1343/A5738), the University of Birmingham and the Birmingham and The Black Country and West Midlands North and South Comprehensive Local Research Networks. Sequencing and arrays were funded by philanthropic donations to the Bladder Cancer Research Centre at the University of Birmingham. B Noyvert was funded through the Cancer Research UK Birmingham Centre award C17422/A25154. We gratefully acknowledge the contribution made by the University of Birmingham’s Human Biomaterials Resource Centre supported through the Birmingham Science City – Experimental Medicine Network of Excellence project. Sequencing was carried out by Genomics Birmingham, Department of Experimental Medicine, University of Birmingham, UK. We are grateful to the urologists and urology nurses of the West Midlands for the recruitment and follow-up of BCPP participants. The work described in this paper used the CaStLeS infrastructure at the University of Birmingham.
© 2022, The Author(s).
- Urothelial carcinoma
- Bladder cancer
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
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1/03/19 → 29/02/20
1/02/19 → 31/01/20
1/04/17 → 31/03/22