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

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An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer. / Lindskrog, Sia Viborg; Prip, Frederik; Lamy, Philippe; Taber, Ann; Groeneveld, Clarice S.; Birkenkamp-Demtröder, Karin; Jensen, Jørgen Bjerggaard; Strandgaard, Trine; Nordentoft, Iver; Christensen, Emil; Sokac, Mateo; Birkbak, Nicolai J.; Maretty, Lasse; Hermann, Gregers G.; Petersen, Astrid C.; Weyerer, Veronika; Grimm, Marc Oliver; Horstmann, Marcus; Sjödahl, Gottfrid; Höglund, Mattias; Steiniche, Torben; Mogensen, Karin; de Reyniès, Aurélien; Nawroth, Roman; Jordan, Brian; Lin, Xiaoqi; Dragicevic, Dejan; Ward, Douglas G.; Goel, Anshita; Hurst, Carolyn D.; Raman, Jay D.; Warrick, Joshua I.; Segersten, Ulrika; Sikic, Danijel; van Kessel, Kim E.M.; Maurer, Tobias; Meeks, Joshua J.; DeGraff, David J.; Bryan, Richard T.; Knowles, Margaret A.; Simic, Tatjana; Hartmann, Arndt; Zwarthoff, Ellen C.; Malmström, Per Uno; Malats, Núria; Real, Francisco X.; Dyrskjøt, Lars.

I: Nature Communications, Bind 12, Nr. 1, 2301, 2021.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

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, bind 12, nr. 1, 2301. https://doi.org/10.1038/s41467-021-22465-w

APA

CBE

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. 12(1):Article 2301. https://doi.org/10.1038/s41467-021-22465-w

MLA

Vancouver

Author

Lindskrog, Sia Viborg ; Prip, Frederik ; Lamy, Philippe ; Taber, Ann ; Groeneveld, Clarice S. ; Birkenkamp-Demtröder, Karin ; Jensen, Jørgen Bjerggaard ; Strandgaard, Trine ; Nordentoft, Iver ; Christensen, Emil ; Sokac, Mateo ; Birkbak, Nicolai J. ; Maretty, Lasse ; Hermann, Gregers G. ; Petersen, Astrid C. ; Weyerer, Veronika ; Grimm, Marc Oliver ; Horstmann, Marcus ; Sjödahl, Gottfrid ; Höglund, Mattias ; Steiniche, Torben ; Mogensen, Karin ; de Reyniès, Aurélien ; Nawroth, Roman ; Jordan, Brian ; Lin, Xiaoqi ; Dragicevic, Dejan ; Ward, Douglas G. ; Goel, Anshita ; Hurst, Carolyn D. ; Raman, Jay D. ; Warrick, Joshua I. ; Segersten, Ulrika ; Sikic, Danijel ; van Kessel, Kim E.M. ; Maurer, Tobias ; Meeks, Joshua J. ; DeGraff, David J. ; Bryan, Richard T. ; Knowles, Margaret A. ; Simic, Tatjana ; Hartmann, Arndt ; Zwarthoff, Ellen C. ; Malmström, Per Uno ; Malats, Núria ; Real, Francisco X. ; Dyrskjøt, Lars. / An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer. I: Nature Communications. 2021 ; Bind 12, Nr. 1.

Bibtex

@article{4b15a1768c1640a9a6de0dc742db0558,
title = "An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer",
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.",
author = "Lindskrog, {Sia Viborg} and Frederik Prip and Philippe Lamy and Ann Taber and Groeneveld, {Clarice S.} and Karin Birkenkamp-Demtr{\"o}der and Jensen, {J{\o}rgen Bjerggaard} and Trine Strandgaard and Iver Nordentoft and Emil Christensen and Mateo Sokac and Birkbak, {Nicolai J.} and Lasse Maretty and Hermann, {Gregers G.} and Petersen, {Astrid C.} and Veronika Weyerer and Grimm, {Marc Oliver} and Marcus Horstmann and Gottfrid Sj{\"o}dahl and Mattias H{\"o}glund and Torben Steiniche and Karin Mogensen and {de Reyni{\`e}s}, Aur{\'e}lien and Roman Nawroth and Brian Jordan and Xiaoqi Lin and Dejan Dragicevic and Ward, {Douglas G.} and Anshita Goel and Hurst, {Carolyn D.} and Raman, {Jay D.} and Warrick, {Joshua I.} and Ulrika Segersten and Danijel Sikic and {van Kessel}, {Kim E.M.} and Tobias Maurer and Meeks, {Joshua J.} and DeGraff, {David J.} and Bryan, {Richard T.} and Knowles, {Margaret A.} and Tatjana Simic and Arndt Hartmann and Zwarthoff, {Ellen C.} and Malmstr{\"o}m, {Per Uno} and N{\'u}ria Malats and Real, {Francisco X.} and Lars Dyrskj{\o}t",
note = "Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
doi = "10.1038/s41467-021-22465-w",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer

AU - Lindskrog, Sia Viborg

AU - Prip, Frederik

AU - Lamy, Philippe

AU - Taber, Ann

AU - Groeneveld, Clarice S.

AU - Birkenkamp-Demtröder, Karin

AU - Jensen, Jørgen Bjerggaard

AU - Strandgaard, Trine

AU - Nordentoft, Iver

AU - Christensen, Emil

AU - Sokac, Mateo

AU - Birkbak, Nicolai J.

AU - Maretty, Lasse

AU - Hermann, Gregers G.

AU - Petersen, Astrid C.

AU - Weyerer, Veronika

AU - Grimm, Marc Oliver

AU - Horstmann, Marcus

AU - Sjödahl, Gottfrid

AU - Höglund, Mattias

AU - Steiniche, Torben

AU - Mogensen, Karin

AU - de Reyniès, Aurélien

AU - Nawroth, Roman

AU - Jordan, Brian

AU - Lin, Xiaoqi

AU - Dragicevic, Dejan

AU - Ward, Douglas G.

AU - Goel, Anshita

AU - Hurst, Carolyn D.

AU - Raman, Jay D.

AU - Warrick, Joshua I.

AU - Segersten, Ulrika

AU - Sikic, Danijel

AU - van Kessel, Kim E.M.

AU - Maurer, Tobias

AU - Meeks, Joshua J.

AU - DeGraff, David J.

AU - Bryan, Richard T.

AU - Knowles, Margaret A.

AU - Simic, Tatjana

AU - Hartmann, Arndt

AU - Zwarthoff, Ellen C.

AU - Malmström, Per Uno

AU - Malats, Núria

AU - Real, Francisco X.

AU - Dyrskjøt, Lars

N1 - Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85104378401&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-22465-w

DO - 10.1038/s41467-021-22465-w

M3 - Journal article

C2 - 33863885

AN - SCOPUS:85104378401

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2301

ER -