An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

引用：Lindskrog SV, Prip F, Lamy P, Taber A, Groeneveld CS, Birkenkamp-Demtröder K, Jensen JB, Strandgaard T, Nordentoft I, Christensen E, Sokac M, Birkbak NJ, Maretty L, Hermann GG, Petersen AC, Weyerer V, Grimm MO, Horstmann M, Sjödahl G, Höglund M, Steiniche T, Mogensen K, de Reyniès A, Nawroth R, Jordan B, Lin X, Dragicevic D, Ward DG, Goel A, Hurst CD, Raman JD, Warrick JI, Segersten U, Sikic D, van Kessel KEM, Maurer T, Meeks JJ, DeGraff DJ, Bryan RT, Knowles MA, Simic T, Hartmann A, Zwarthoff EC, Malmström PU, Malats N, Real FX, Dyrskjøt L. (2021). An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer. Nature communications. PMID 33863885 · PMC8052448 · DOI 10.1038/s41467-021-22465-w

证据类型：PRIMARY_RESEARCH

主题：rna-seq、multi-omics

被引次数（采集时）：291

原始记录：[Europe PMC](https://europepmc.org/article/MED/33863885)

来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

作者摘要（按来源许可复用）

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.

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