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

Adele M Alchahin1, Shenglin Mei2, Ioanna Tsea1

  • 1Childhood Cancer Research unit, Department of Children's and Women's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Nature Communications
|September 30, 2022
PubMed

Insights

Researchers identified a unique transcriptional signature in primary clear cell renal cell carcinoma (ccRCC) that predicts metastatic potential. This discovery offers new therapeutic targets for this lethal kidney cancer.

Area of Science:

  • Oncology
  • Genomics
  • Translational Medicine

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer.
  • Localized ccRCC is often curable, but metastatic ccRCC remains a lethal disease.

Purpose of the Study:

  • To identify transcriptional signatures in primary ccRCC that predict metastatic potential.
  • To investigate the tumor microenvironment and identify potential therapeutic targets in metastatic ccRCC.

Main Methods:

  • Single-cell transcriptomic analysis of fresh patient samples (primary tumors, normal kidney tissue, bone metastases).
  • In silico cell-to-cell interaction analysis.

Main Results:

  • A distinct transcriptional signature in primary ccRCC tumor cells predicts metastatic potential and patient survival.
  • Vascular remodeling was observed in endothelial cells within the tumor microenvironment.
  • The CXCL9/CXCL10-CXCR3 and CD70-CD27 axes were identified as potential therapeutic targets.

Conclusions:

  • The study provides biological insights into ccRCC tumor cell and microenvironment interactions.
  • Identified transcriptional signatures and molecular axes offer potential therapeutic strategies for metastatic ccRCC.