Multiomics Profiling of Urothelial Carcinoma In Situ Reveals Cis-Specific Gene Signature and Immune Characteristics

Authors

• Meenakshi Anurag
• Trine Strandgaard
• Sung Han Kim
• Yongchao Dou
• Eva Comperat
• Hikmat Al-Ahmadie
• Brant A Inman
• Ann Taber
• Iver Nordentoft
• Jørgen Bjerggaard Jensen
• Lars Dyrskjøt
• Seth P Lerner

Language

English

Publication Date

3-15-2024

Journal

iScience

DOI

10.1016/j.isci.2024.109179

PMID

38439961

PMCID

PMC10910238

PubMedCentral® Posted Date

2-9-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Urothelial carcinoma in situ (CIS) is an aggressive phenotype of non-muscle-invasive bladder cancer. Molecular features unique to CIS compared to high-grade papillary tumors are underexplored. RNA sequencing of CIS, papillary tumors, and normal urothelium showed lower immune marker expression in CIS compared to papillary tumors. We identified a 46-gene expression signature in CIS samples including selectively upregulated known druggable targets MTOR, TYK2, AXIN1, CPT1B, GAK, and PIEZO1 and selectively downregulated BRD2 and NDUFB2. High expression of selected genes was significantly associated with CIS in an independent dataset. Mutation analysis of matched CIS and papillary tumors revealed shared mutations between samples across time points and mutational heterogeneity. CCDC138 was the most frequently mutated gene in CIS. The immunological landscape showed higher levels of PD-1-positive cells in CIS lesions compared to papillary tumors. We identified CIS lesions to have distinct characteristics compared to papillary tumors potentially contributing to the aggressive phenotype.

Keywords

Immunology, Cancer, Omics

Published Open-Access

yes

Recommended Citation

Anurag, Meenakshi; Strandgaard, Trine; Kim, Sung Han; et al., "Multiomics Profiling of Urothelial Carcinoma In Situ Reveals Cis-Specific Gene Signature and Immune Characteristics" (2024). Faculty, Staff and Students Publications. 7961.
https://digitalcommons.library.tmc.edu/baylor_docs/7961