Multiomics profiling of urothelial carcinoma in situ reveals CIS-specific gene signature and immune characteristics

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*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


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.

Original languageEnglish
Article number109179
Publication statusPublished - 15 Mar 2024


  • Cancer
  • Immunology
  • Omics


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