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  3. The integrate profiling of single-cell and spatial transcriptome RNA-seq reveals tumor heterogeneity, therapeutic targets, and prognostic subtypes in ccRCC

The integrate profiling of single-cell and spatial transcriptome RNA-seq reveals tumor heterogeneity, therapeutic targets, and prognostic subtypes in ccRCC

  • Cancer Gene Ther. 2024 Mar 13. doi: 10.1038/s41417-024-00755-x.
Yanlong Zhang # 1 2 3 4 5 6,  Xuefeng Huang # 1 3 4 5,  Minghang Yu # 1 3 4 5,  Menghan Zhang 1,  Li Zhao 2,  Yong Yan 7,  Liyun Zhang 8,  Xi Wang 9 10 11 12
Affiliations

Affiliations

  • 1 National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
  • 2 Shanxi Medical University, Shanxi Bethune Hospital, Taiyuan, Shanxi, China.
  • 3 Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
  • 4 Beijing Institute of Infectious Diseases, Beijing, 100015, China.
  • 5 National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
  • 6 Department of Urology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
  • 7 Department of Urology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China. yanyongsjt@163.com.
  • 8 Shanxi Medical University, Shanxi Bethune Hospital, Taiyuan, Shanxi, China. 1315710223@qq.com.
  • 9 National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China. xiwang@ccmu.edu.cn.
  • 10 Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China. xiwang@ccmu.edu.cn.
  • 11 Beijing Institute of Infectious Diseases, Beijing, 100015, China. xiwang@ccmu.edu.cn.
  • 12 National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China. xiwang@ccmu.edu.cn.
  • # Contributed equally.
PMID: 38480978 DOI: 10.1038/s41417-024-00755-x
Abstract

Clear-cell renal cell carcinoma (ccRCC) is the most common type of RCC; however, the intratumoral heterogeneity in ccRCC remains unclear. We first identified markers and biological features of each cell cluster using bioinformatics analysis based on single-cell and spatial transcriptome RNA-sequencing data. We found that gene copy number loss on chromosome 3p and amplification on chromosome 5q were common features in ccRCC cells. Meanwhile, NNMT and HILPDA, which are associated with the response to hypoxia and metabolism, are potential therapeutic targets for ccRCC. In addition, CD8+ exhausted T cells (LAG3+ HAVCR2+), CD8+ proliferated T cells (STMN+), and M2-like macrophages (CD68+ CD163+ APOC1+), which are closely associated with immunosuppression, played vital roles in ccRCC occurrence and development. These results were further verified by whole exome sequencing, cell line and xenograft experiments, and immunofluorescence staining. Finally, we divide patients with ccRCC into three subtypes using unsupervised cluster analysis. and generated a classifier to reproduce these subtypes using the eXtreme Gradient Boosting algorithm. Our classifier can help clinicians evaluate prognosis and design personalized treatment strategies for ccRCC. In summary, our work provides a new perspective for understanding tumor heterogeneity and will aid in the design of antitumor therapeutic strategies for ccRCC.

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