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  • Marklund, MajaKTH,Genteknologi,Science for Life Laboratory, SciLifeLab (author)

Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-09-17
  • Springer Nature,2022
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-319836
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-319836URI
  • https://doi.org/10.1038/s41467-022-33069-3DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-210281URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:150723326URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20221012
  • The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyze tumor heterogeneity in needle biopsies collected before and after treatment with androgen deprivation therapy. By doing so, we are able to couple clinical responsiveness and morphological information such as Gleason score to transcriptome-wide data. Our data-driven analysis of transcriptomes identifies several distinct intratumoral cell populations, characterized by their unique gene expression profiles. Certain cell populations present before treatment exhibit gene expression profiles that match those of resistant tumor cell clusters, present after treatment. We confirm that these clusters are resistant by the localization of active androgen receptors to the nuclei in cancer cells post-treatment. Our data also demonstrates that most stromal cells adjacent to resistant clusters do not express the androgen receptor, and we identify differentially expressed genes for these cells. Altogether, this study shows the potential to increase the power in predicting resistant tumors. Spatial heterogeneity in prostate cancer can contribute to its resistance to androgen deprivation therapy (ADT). Here, the authors analyse prostate cancer samples before and after ADT using Spatial Transcriptomics, and find heterogeneous pre-treatment tumour cell populations and stromal cells that are associated with resistance.

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  • Schultz, NiklasKarolinska Institutet (author)
  • Friedrich, Stefanie,1973-Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Stockholm Univ, Dept Biochem & Biophys, Sci Lab, Solna, Sweden.(Swepub:su)stfr6041 (author)
  • Berglund, EmelieKTH,Genteknologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u19v38i6 (author)
  • Tarish, FirasKarolinska Inst, Div Translat Med & Chem Biol, Sci Life Lab, Solna, Sweden. (author)
  • Tanoglidi, AnnaEvangelismos Gen Hosp, Dept Pathol, 45-47 Ipsilantou Str, Athens, Greece. (author)
  • Liu, YaoKarolinska Inst, Div Translat Med & Chem Biol, Sci Life Lab, Solna, Sweden. (author)
  • Bergenstråhle, LudvigKTH,Genteknologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1f4ltny (author)
  • Erickson, AndrewUniv Oxford, Nuffield Dept Surg Sci, Oxford, England. (author)
  • Helleday, ThomasKarolinska Institutet (author)
  • Lamb, Alastair D.Univ Oxford, Nuffield Dept Surg Sci, Oxford, England. (author)
  • Sonnhammer, Erik L. L.Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Stockholm Univ, Dept Biochem & Biophys, Sci Lab, Solna, Sweden.(Swepub:su)esonn (author)
  • Lundeberg, JoakimKTH,Science for Life Laboratory, SciLifeLab,Genteknologi(Swepub:kth)u1qkn9kw (author)
  • KTHGenteknologi (creator_code:org_t)

Related titles

  • In:Nature Communications: Springer Nature13:12041-1723

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