open access publication

Article, 2024

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

iScience, ISSN 2589-0042, Volume 27, 3, Page 109179, 10.1016/j.isci.2024.109179

Contributors

Anurag, Meenakshi 0000-0003-4379-5192 [1] Strandgaard, Trine 0000-0001-8277-8155 [2] [3] Kim, Sung Han 0000-0002-1689-5203 [4] [5] Dou, Yongchao [1] Compérat, Eva Maria 0000-0001-8488-543X [6] [7] Al-Ahmadie, Hikmat A 0000-0002-2938-6627 [8] Inman, Brant Allen 0000-0002-6060-4485 [9] Taber, Ann [2] [3] Nordentoft, Iver K 0000-0003-4856-4086 [3] Jensen, Jørgen Bjerggaard 0000-0002-4347-739X [2] [3] Dyrskjøt, Lars 0000-0001-7061-9851 (Corresponding author) [2] [3] Lerner, Seth Paul 0000-0002-6379-2581 (Corresponding author) [5]

Affiliations

  1. [1] Baylor College of Medicine
    2. [NORA names: United States; America, North; OECD];
  2. [2] Aarhus University Hospital
    3. [NORA names: Central Denmark Region; Hospital; Denmark; Europe, EU; Nordic; OECD];
  3. [3] Aarhus University
    4. [NORA names: AU Aarhus University; University; Denmark; Europe, EU; Nordic; OECD];
  4. [4] National Cancer Center
    5. [NORA names: South Korea; Asia, East; OECD];
  5. [5] Dan L Duncan Comprehensive Cancer Center
    6. [NORA names: United States; America, North; OECD];

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

CIS lesions, CIS samples, PD-1-positive cells, RNA, RNA sequencing, aggressive phenotype, associated with CIS, bladder cancer, cancer, carcinoma in situ, cells, characteristics, cis, dataset, expression, expression signatures, gene signature, genes, heterogeneity, higher expression, immune characteristics, immune marker expression, immunological landscape, independent datasets, landscape, lesions, levels, marker expression, multiomic profiling, multiomics, mutated genes, mutation analysis, mutational heterogeneity, mutations, non-muscle-invasive bladder cancer, papillary tumors, phenotype, point, samples, signature, time, time points, tumor, urothelial carcinoma in situ

Funders

  • National Cancer Institute
  • AstraZeneca (United States)
  • Bristol-Myers Squibb (United States)
  • MSD (United States)
  • Pfizer (United States)
  • Roche (United States)

Data Provider: Digital Science

LINKS
-

Matching Records in NORA

SUBJECTS
+

METRICS
+