PT  - JOURNAL ARTICLE
AU  - Adele M. Alchahin
AU  - Shenglin Mei
AU  - Ioanna Tsea
AU  - Taghreed Hirz
AU  - Youmna Kfoury
AU  - Douglas Dahl
AU  - Chin-Lee Wu
AU  - Alexander O. Subtelny
AU  - Shulin Wu
AU  - David T. Scadden
AU  - John H. Shin
AU  - Philip J. Saylor
AU  - David B. Sykes
AU  - Peter V. Kharchenko
AU  - Ninib Baryawno
TI  - A new transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma
AID  - 10.1101/2022.06.28.497333
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.28.497333
4099  - http://biorxiv.org/content/early/2022/07/01/2022.06.28.497333.short
4100  - http://biorxiv.org/content/early/2022/07/01/2022.06.28.497333.full
AB  - 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 take advantage of 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 revealed a distinct transcriptional signature that was predictive of metastatic potential and patient survival. Analysis of supporting stromal cells within the tumor environment demonstrated vascular remodeling within the endothelial cells and a proliferative signature within the fibroblasts that was associated with poor survival. An in silico cell-to-cell interaction analysis highlighted 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.Competing Interest StatementP.V.K. serves on the Scientific Advisory Board to Celsius Therapeutics Inc. and Biomage Inc. D.T.S. is a director and shareholder for Agios Therapeutics and Editas Medicines; a founder, director, shareholder, and scientific advisory board member for Magenta Therapeutics and LifeVault Bio, a shareholder and founder of Fate Therapeutics, and a director, founder, and shareholder for Clear Creek Bio, a consultant for FOG Pharma and VCanBio, and a recipient of sponsored research funding from Novartis. D.B.S. is a founder, consultant, and shareholder for Clear Creek Bio.