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  • Viborg Lindskrog, SiaAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, Denmark,Aarhus University Hospital (författare)

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

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-04-16
  • Springer Nature,2021
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-443195
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-443195URI
  • https://doi.org/10.1038/s41467-021-22465-wDOI
  • https://lup.lub.lu.se/record/9097e5ff-635e-4a49-ba63-c7ee9f1bf16eURI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Prip, FrederikAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, Denmark,Aarhus University Hospital (författare)
  • Lamy, PhilippeAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark,Aarhus University Hospital (författare)
  • Taber, AnnAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, Denmark,Aarhus University Hospital (författare)
  • Groeneveld, Clarice S.Ligue Natl Canc, Cartes Identite Tumeurs CIT Program, Paris, France; Inst Curie, UMR144, Oncol Mol, Paris, France,Curie Institute, Paris,Ligue Nationale Contre le Cancer (författare)
  • Birkenkamp-Demtröder, KarinAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, Denmark,Aarhus University Hospital (författare)
  • Bjerggaard Jensen, JørgenAarhus Univ, Dept Clin Med, Aarhus, Denmark; Aarhus Univ Hosp, Dept Urol, Aarhus N, Denmark,Aarhus University Hospital (författare)
  • Strandgaard, TrineAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, Denmark,Aarhus University Hospital (författare)
  • Nordentoft, IverAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark,Aarhus University Hospital (författare)
  • Christensen, EmilAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, Denmark,Aarhus University Hospital (författare)
  • Sokac, MateoAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, Denmark,Aarhus University Hospital (författare)
  • Birkbak, Nicolai J.Aarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, Denmark,Aarhus University Hospital (författare)
  • Maretty, LasseAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, Denmark,Aarhus University Hospital (författare)
  • Hermann, Gregers G.Univ Copenhagen, Herlev Hosp, Dept Urol, Copenhagen, Denmark,University of Copenhagen (författare)
  • Petersen, Astrid C.Aalborg Univ Hosp, Dept Pathol, Aalborg, Denmark,Aalborg University Hospital (författare)
  • Weyerer, VeronikaFriedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany,University Hospital Erlangen (författare)
  • Grimm, Marc-OliverJena Univ Hosp, Dept Urol, Jena, Germany,Universitätsklinikum Jena (författare)
  • Horstmann, MarcusJena Univ Hosp, Dept Urol, Jena, Germany; St Josephshosp, Dept Urol, Malteser Hosp, Krefeld, Germany,St. Josefs Hospital Uerdingen,Universitätsklinikum Jena (författare)
  • Sjödahl, GottfridLund University,Lunds universitet,Urologi - blåscancer, Malmö,Forskargrupper vid Lunds universitet,Genomiska analyser av urinblåscancer,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urinblåsecancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Urology - urothelial cancer, Malmö,Lund University Research Groups,Urothelial Cancer Genomics,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Urothelial cancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Univ, Skane Univ Hosp, Dept Translat Med, Div Urol Res, Malmö, Sweden(Swepub:lu)med-gsj (författare)
  • Höglund, MattiasLund University,Lunds universitet,Genomiska analyser av urinblåscancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urinblåsecancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Urothelial Cancer Genomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Urothelial cancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden(Swepub:lu)kgen-mho (författare)
  • Steiniche, TorbenAarhus Univ Hosp, Dept Pathol, Aarhus N, Denmark,Aarhus University Hospital (författare)
  • Mogensen, KarinUniv Copenhagen, Herlev Hosp, Dept Urol, Copenhagen, Denmark,University of Copenhagen (författare)
  • de Reyniès, AurélienLigue Natl Canc, Cartes Identite Tumeurs CIT Program, Paris, France,Ligue Nationale Contre le Cancer (författare)
  • Nawroth, RomanTech Univ Munich, Dept Urol, Klinikum Rechts Isar, Munich, Germany (författare)
  • Jordan, BrianNorthwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA.;Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA.;Northwestern Univ, Sch Med, Dept Biochem, Chicago, IL USA.;Northwestern Univ, Sch Med, Dept Mol Genet, Chicago, IL USA,Northwestern University Feinberg School of Medicine (författare)
  • Lin, XiaoqiNorthwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA.;Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA.;Northwestern Univ, Sch Med, Dept Biochem, Chicago, IL USA.;Northwestern Univ, Sch Med, Dept Mol Genet, Chicago, IL USA,Northwestern University Feinberg School of Medicine (författare)
  • Dragicevic, DejanUniv Belgrade, Fac Med, Clin Ctr Serbia, Clin Urol, Belgrade, Serbia,University of Belgrade,Leeds School of Medicine,Pennsylvania State University,Univ Leeds, Leeds Inst Med Res St James's, Leeds, W Yorkshire, England,Penn State Univ, Dept Surg, Div Urol, Hershey, PA USA (författare)
  • Ward, Douglas G.Univ Birmingham, Coll Med & Dent Sci, Bladder Canc Res Ctr, Inst Canc & Genom Sci, Birmingham, W Midlands, England,University of Birmingham (författare)
  • Goel, AnshitaUniv Birmingham, Coll Med & Dent Sci, Bladder Canc Res Ctr, Inst Canc & Genom Sci, Birmingham, W Midlands, England,University of Birmingham (författare)
  • Hurst, Carolyn D.Univ Leeds, Leeds Inst Med Res St James's, Leeds, W Yorkshire, England (författare)
  • Raman, Jay D.Penn State Univ, Dept Surg, Div Urol, Hershey, PA USA (författare)
  • Warrick, Joshua I.Penn State Univ, Dept Biochem & Mol Biol, Dept Pathol & Lab Med, Div Urol, Hershey, PA USA,Pennsylvania State University (författare)
  • Segersten, UlrikaUppsala University,Uppsala universitet,Urologkirurgi(Swepub:uu)ulriande (författare)
  • Sikic, DanijelFriedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Dept Urol & Pediat Urol, Erlangen, Germany,University Hospital Erlangen (författare)
  • van Kessel, Kim E. M.Erasmus MC, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands,Erasmus University Medical Center (författare)
  • Maurer, TobiasTech Univ Munich, Dept Urol, Klinikum Rechts Isar, Munich, Germany; Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany.;Univ Med Ctr Hamburg Eppendorf, Martini Clin, Hamburg, Germany,University Medical Center Hamburg-Eppendorf (författare)
  • Meeks, Joshua J.Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA.;Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA.;Northwestern Univ, Sch Med, Dept Biochem, Chicago, IL USA.;Northwestern Univ, Sch Med, Dept Mol Genet, Chicago, IL USA,Northwestern University Feinberg School of Medicine (författare)
  • DeGraff, David J.Penn State Univ, Dept Biochem & Mol Biol, Dept Pathol & Lab Med, Div Urol, Hershey, PA USA,Pennsylvania State University (författare)
  • Bryan, Richard T.Univ Birmingham, Coll Med & Dent Sci, Bladder Canc Res Ctr, Inst Canc & Genom Sci, Birmingham, W Midlands, England,University of Birmingham (författare)
  • Knowles, Margaret A.Univ Leeds, Leeds Inst Med Res St James's, Leeds, W Yorkshire, England,Leeds School of Medicine (författare)
  • Simic, TatjanaUniv Belgrade, Fac Med, Inst Med & Clin Biochem, Belgrade, Serbia,University of Belgrade (författare)
  • Hartmann, ArndtFriedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany,University Hospital Erlangen (författare)
  • Zwarthoff, Ellen C.Erasmus MC, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands,Erasmus University Medical Center (författare)
  • Malmström, Per-UnoUppsala University,Uppsala universitet,Urologkirurgi(Swepub:uu)perunoms (författare)
  • Malats, NúriaCIBERONC, Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain,Spanish National Cancer Research Center (CNIO) (författare)
  • Real, Francisco X.Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid, Spain; Univ Pompeu Fabra, Dept Ciencies Expt & Salut, CIBERONC, Barcelona, Spain,Pompeu Fabra University,Spanish National Cancer Research Center (CNIO) (författare)
  • Dyrskjøt, LarsAarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, Denmark,Aarhus University Hospital (författare)
  • Aarhus Univ Hosp, Dept Mol Med, Aarhus N, Denmark; Aarhus Univ, Dept Clin Med, Aarhus, DenmarkAarhus University Hospital (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Nature Communications: Springer Nature12:12041-1723

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