期刊
CELL
卷 184, 期 11, 页码 2988-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2021.04.038
关键词
-
资金
- National Cancer Institute's Office of Cancer Genomics Cancer Target Discovery and Development (CTD2) initiative
- National Institutes of Health (NIH) [R01 CA127153, 1P50CA58236-15, P30CA006973]
- CUMC institutional funds
- NIH [R35CA197745, U01DA217858, S10 OD012351, S10 OD021764]
- NIH grant R38 grant [CA231577]
- DOD/CDMRP award [W81XWH-17-10309, CA160728]
- [P30CA013696]
- CDMRP [917423, CA160728] Funding Source: Federal RePORTER
This study identified specific subpopulations and their master regulators through single-cell RNA sequencing, and found that TREM2/APOE/C1Q-positive macrophage infiltration could serve as a potential prognostic biomarker for ccRCC recurrence.
Clear cell renal carcinoma (ccRCC) is a heterogeneous disease with a variable post-surgical course. To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performed single-cell RNA sequencing (scRNA-seq) of hematopoietic and non-hematopoietic subpopulations from tumor and tumor-adjacent tissue of treatment-naive ccRCC resections. We leveraged the VIPER algorithm to quantitate single-cell protein activity and validated this approach by comparison to flow cytometry. The analysis identified key TME subpopulations, as well as their master regulators and candidate cell-cell interactions, revealing clinically relevant populations, undetectable by gene-expression analysis. Specifically, we uncovered a tumor-specific macrophage subpopulation characterized by upregulation of TREM2/APOE/C1Q, validated by spatially resolved, quantitative multispectral immunofluorescence. In a large clinical validation cohort, these markers were significantly enriched in tumors from patients who recurred following surgery. The study thus identifies TREM2/APOE/C1Q-positive macrophage infiltration as a potential prognostic biomarker for ccRCC recurrence, as well as a candidate therapeutic target.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据