期刊
ONCOTARGETS AND THERAPY
卷 13, 期 -, 页码 10453-10464出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S272553
关键词
renal cell carcinoma; CD39; prognosis; TCGA; infiltrating immune cells; immune checkpoint therapy
资金
- National Natural Science Foundation of China [81772706]
Introduction: The cell-surface ectonucleotidase CD39 is a key molecule of the immunosuppressive adenosine pathway within the tumor microenvironment. However, the relationship between CD39 and clear cell renal cell carcinoma (ccRCC) is rarely reported and still remains unclear. Methods: CD39 expression was first analyzed using the Oncomine and the Tumor IMmune Estimation Resource (TIMER) databases, and then examined in ccRCC patients (n=367) who had undergone radical nephrectomy using immunohistochemistry (IHC) and real-time quantitative PCR analysis (qPCR). The prognosis value of CD39 in ccRCC was evaluated by Cox proportional hazards analysis. Functional and gene set enrichment analysis (GSEA) was performed using transcriptomic data of ccRCC from TCGA. Correlation analysis between CD39 and tumor-infiltrating lymphocytes (TILs) was performed using the TISIDB database. The impact of CD39 on immune checkpoint therapy (ICT) was evaluated by two public cohorts. Results: CD39 mRNA and protein expression was upregulated in tumor tissues from ccRCC patients and aberrant expression of CD39 was associated with advanced tumor stage and poor prognosis in ccRCC patients. EMT, IL-2/STAT5, inflammatory response, interferon gamma and KRAS hallmark gene sets were identified as CD39-related signaling pathway. The expression level of CD39 was significantly and positively correlated with high abundance of the regulatory TILs including NK cells, macrophages, Th cells and Treg cells. CD39 was correlated with expression of several immune checkpoints and higher CD39 expression was associated with better OS of ccRCC patients who received ICT. Conclusion: CD39 is a powerful prognostic marker of ccRCC patients. Increased tumor expression of CD39 mRNA is significantly correlated with infiltrating levels of TILs, and better efficacy of ICT to ccRCC. CD39 could be a novel therapeutic target for ccRCC.
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