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An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer
- Source :
- Nature Communications, Lindskrog, S V, Prip, F, Lamy, P, Taber, A, Groeneveld, C S, Birkenkamp-Demtröder, K, Jensen, J B, Strandgaard, T, Nordentoft, I, Christensen, E, Sokac, M, Birkbak, N J, Maretty, L, Hermann, G G, Petersen, A C, Weyerer, V, Grimm, M O, Horstmann, M, Sjödahl, G, Höglund, M, Steiniche, T, Mogensen, K, de Reyniès, A, Nawroth, R, Jordan, B, Lin, X, Dragicevic, D, Ward, D G, Goel, A, Hurst, C D, Raman, J D, Warrick, J I, Segersten, U, Sikic, D, van Kessel, K E M, Maurer, T, Meeks, J J, DeGraff, D J, Bryan, R T, Knowles, M A, Simic, T, Hartmann, A, Zwarthoff, E C, Malmström, P U, Malats, N, Real, F X & Dyrskjøt, L 2021, ' An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer ', Nature Communications, vol. 12, no. 1, 2301 . https://doi.org/10.1038/s41467-021-22465-w, Nature Communications, 12(1):2301. Nature Publishing Group, Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.<br />Multiple molecular profiling methods are required to study urothelial non-muscle-invasive bladder cancer (NMIBC) due to its heterogeneity. Here the authors integrate multi-omics data of 834 NMIBC patients, identifying a molecular subgroup associated with multiple alterations and worse outcomes.
- Subjects :
- Cancer microenvironment
0301 basic medicine
Oncology
medicine.medical_specialty
Science
General Physics and Astronomy
Disease
Biology
Proteomics
Article
General Biochemistry, Genetics and Molecular Biology
Transcriptome
03 medical and health sciences
0302 clinical medicine
SDG 3 - Good Health and Well-being
Internal medicine
Chromosome instability
Urologi och njurmedicin
Cancer genomics
medicine
Urology and Nephrology
Progression-free survival
Biomarker discovery
Cancer och onkologi
Multidisciplinary
Bladder cancer
General Chemistry
medicine.disease
Subtyping
Computational biology and bioinformatics
030104 developmental biology
Cancer and Oncology
030220 oncology & carcinogenesis
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....493302bfc891046f449ef1ccfb5a44cf