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A transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma

Author

Listed:
  • Adele M. Alchahin

    (Karolinska University Hospital)

  • Shenglin Mei

    (Harvard Medical School)

  • Ioanna Tsea

    (Karolinska University Hospital)

  • Taghreed Hirz

    (Massachusetts General Hospital
    Harvard Stem Cell Institute
    Harvard University)

  • Youmna Kfoury

    (Massachusetts General Hospital
    Harvard Stem Cell Institute
    Harvard University)

  • Douglas Dahl

    (Harvard Medical School)

  • Chin-Lee Wu

    (Harvard Medical School)

  • Alexander O. Subtelny

    (Harvard Medical School)

  • Shulin Wu

    (Harvard Medical School)

  • David T. Scadden

    (Massachusetts General Hospital
    Harvard Stem Cell Institute
    Harvard University)

  • John H. Shin

    (Harvard Medical School)

  • Philip J. Saylor

    (Harvard Medical School)

  • David B. Sykes

    (Massachusetts General Hospital
    Harvard Stem Cell Institute
    Harvard University)

  • Peter V. Kharchenko

    (Harvard Medical School
    Harvard Stem Cell Institute
    Altos Labs)

  • Ninib Baryawno

    (Karolinska University Hospital
    Massachusetts General Hospital
    Harvard Stem Cell Institute
    Harvard University)

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer in adults. When ccRCC is localized to the kidney, surgical resection or ablation of the tumor is often curative. However, in the metastatic setting, ccRCC remains a highly lethal disease. Here we use fresh patient samples that include treatment-naive primary tumor tissue, matched adjacent normal kidney tissue, as well as tumor samples collected from patients with bone metastases. Single-cell transcriptomic analysis of tumor cells from the primary tumors reveals a distinct transcriptional signature that is predictive of metastatic potential and patient survival. Analysis of supporting stromal cells within the tumor environment demonstrates vascular remodeling within the endothelial cells. An in silico cell-to-cell interaction analysis highlights the CXCL9/CXCL10-CXCR3 axis and the CD70-CD27 axis as potential therapeutic targets. Our findings provide biological insights into the interplay between tumor cells and the ccRCC microenvironment.

Suggested Citation

  • Adele M. Alchahin & Shenglin Mei & Ioanna Tsea & Taghreed Hirz & Youmna Kfoury & Douglas Dahl & Chin-Lee Wu & Alexander O. Subtelny & Shulin Wu & David T. Scadden & John H. Shin & Philip J. Saylor & D, 2022. "A transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33375-w
    DOI: 10.1038/s41467-022-33375-w
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