An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer.
An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer.
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综合多组学分析确定了非肌肉浸润性膀胱癌的预后分子亚型。
DOI：
10.1038/s41467-021-22465-w
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发表时间：
2021-04-16
影响因子：
16.6
通讯作者：
Dyrskjøt L
中科院分区：
文献类型：
--
作者：
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
非肌层浸润性膀胱癌（NMIBC）的分子景观的特点是具有可变临床结果的大生物异质性。在这里，我们对诊断为NMIBC的患者（n = 834）进行了综合性多组学分析。转录组学分析鉴定了反映肿瘤生物学和疾病侵袭性的四类（1、2a、2b和3）。基于转录组的亚型和染色体不稳定性水平提供了超出既定预后临床病理学参数的独立预后价值。高染色体不稳定性、p53通路破坏和APOBEC相关突变与转录组学2a类和不良结局显著相关。RNA衍生的免疫细胞浸润与染色体不稳定的肿瘤相关，并在2b类中富集。空间蛋白质组学分析证实了2b类肿瘤的较高浸润性，并证明了较高的免疫细胞浸润和较低的复发率之间的关联。最后，独立的预后价值的转录组类记录在1228个验证样本使用单样本分类工具。该分类器为生物标志物发现以及下一代临床试验中的优化治疗和监测提供了一个框架。由于尿路上皮非肌肉浸润性膀胱癌（NMIBC）的异质性，需要多种分子分析方法来研究其。在这里，作者整合了834名NMIBC患者的多组学数据，确定了与多种改变和更差结果相关的分子亚组。
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. 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.
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影响因子：
0.8
作者：
Gagliano A;Pironti E;Cucinotta F;Galati C;Maggio R;Alquino MA;Di Rosa G
通讯作者：
Di Rosa G
影响因子：
8.8
作者：
Dyrskjot, L.;Reinert, T.;Novoradovsky, A.;Zuiverloon, T. C. M.;Beukers, W.;Zwarthoff, E.;Malats, N.;Real, F. X.;Segersten, U.;Malmstrom, P-U;Knowles, M.;Hurst, C.;Sorge, J.;Borre, M.;Orntoft, T. F.
通讯作者：
Orntoft, T. F.
影响因子：
16.6
作者：
Blum, Yuna;Meiller, Clement;Jean, Didier
通讯作者：
Jean, Didier
DOI：
10.1126/science.1253462
发表时间：
2014-10-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Bruin EC;McGranahan N;Mitter R;Salm M;Wedge DC;Yates L;Jamal-Hanjani M;Shafi S;Murugaesu N;Rowan AJ;Grönroos E;Muhammad MA;Horswell S;Gerlinger M;Varela I;Jones D;Marshall J;Voet T;Van Loo P;Rassl DM;Rintoul RC;Janes SM;Lee SM;Forster M;Ahmad T;Lawrence D;Falzon M;Capitanio A;Harkins TT;Lee CC;Tom W;Teefe E;Chen SC;Begum S;Rabinowitz A;Phillimore B;Spencer-Dene B;Stamp G;Szallasi Z;Matthews N;Stewart A;Campbell P;Swanton C
通讯作者：
Swanton C
影响因子：
11.2
作者：
Aaboe, M;Birkenkamp-Demtroder, K;Orntoft, T
通讯作者：
Orntoft, T