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Multiregional transcriptomics identifies congruent consensus subtypes with prognostic value beyond tumor heterogeneity of colorectal cancer

Author

Listed:
  • Jonas Langerud

    (Oslo University Hospital
    University of Oslo)

  • Ina A. Eilertsen

    (Oslo University Hospital)

  • Seyed H. Moosavi

    (Oslo University Hospital)

  • Solveig M. K. Klokkerud

    (Oslo University Hospital
    University of Oslo)

  • Henrik M. Reims

    (Oslo University Hospital)

  • Ingeborg F. Backe

    (Oslo University Hospital
    Oslo University Hospital)

  • Merete Hektoen

    (Oslo University Hospital)

  • Ole H. Sjo

    (Oslo University Hospital)

  • Marine Jeanmougin

    (Oslo University Hospital)

  • Sabine Tejpar

    (Katholieke Universiteit Leuven)

  • Arild Nesbakken

    (University of Oslo
    Oslo University Hospital)

  • Ragnhild A. Lothe

    (Oslo University Hospital
    University of Oslo)

  • Anita Sveen

    (Oslo University Hospital
    University of Oslo)

Abstract

Intra-tumor heterogeneity compromises the clinical value of transcriptomic classifications of colorectal cancer. We investigated the prognostic effect of transcriptomic heterogeneity and the potential for classifications less vulnerable to heterogeneity in a single-hospital series of 1093 tumor samples from 692 patients, including multiregional samples from 98 primary tumors and 35 primary-metastasis sets. We show that intra-tumor heterogeneity of the consensus molecular subtypes (CMS) is frequent and has poor-prognostic associations independently of tumor microenvironment markers. Multiregional transcriptomics uncover cancer cell-intrinsic and low-heterogeneity signals that recapitulate the intrinsic CMSs proposed by single-cell sequencing. Further subclassification identifies congruent CMSs that explain a larger proportion of variation in patient survival than intra-tumor heterogeneity. Plasticity is indicated by discordant intrinsic phenotypes of matched primary and metastatic tumors. We conclude that multiregional sampling reconciles the prognostic power of tumor classifications from single-cell and bulk transcriptomics in the context of intra-tumor heterogeneity, and phenotypic plasticity challenges the reconciliation of primary and metastatic subtypes.

Suggested Citation

  • Jonas Langerud & Ina A. Eilertsen & Seyed H. Moosavi & Solveig M. K. Klokkerud & Henrik M. Reims & Ingeborg F. Backe & Merete Hektoen & Ole H. Sjo & Marine Jeanmougin & Sabine Tejpar & Arild Nesbakken, 2024. "Multiregional transcriptomics identifies congruent consensus subtypes with prognostic value beyond tumor heterogeneity of colorectal cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48706-2
    DOI: 10.1038/s41467-024-48706-2
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