CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
基于溶酶体相关基因识别肾透明细胞癌不同亚型间的免疫特征以辅助免疫治疗
英文原题：Identification of immune characteristics between different subtypes in kidney renal clear cell carcinoma based on lysosome-related genes to assist immunotherapy.
查看英文原题
Identification of immune characteristics between different subtypes in kidney renal clear cell carcinoma based on lysosome-related genes to assist immunotherapy.
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中文摘要
既往研究揭示了溶酶体在人类疾病（包括癌症）中的重要作用，但针对其在肾透明细胞癌（KIRC）中的功能，仍缺乏深入、系统的研究。
本研究收集KIRC公共数据集，筛选出与生存密切相关的溶酶体基因。聚类分析显示，这些基因具有良好分类能力，可将KIRC患者划分为生存率不同的多个亚型。对生存差异最大的两个代表性亚群（cluster1和cluster2）中差异表达基因（DEG）的富集分析发现，主要相关生物过程包括类固醇代谢、中性粒细胞胞外诱捕网形成和酪氨酸代谢。免疫相关分析显示，两个亚群的免疫细胞浸润水平存在显著差异：cluster1中滤泡辅助性T细胞（Tfh）和TIL（肿瘤浸润淋巴细胞）浸润较高；cluster2中II型干扰素应答、肥大细胞和嗜碱性粒细胞浸润较高。免疫治疗相关分析显示，由于cluster1免疫检查点表达、ESTIMATE评分、免疫评分和免疫表型评分（IPS）较高，该亚群可能对免疫治疗更敏感，也更可能获益。
此外，两种亚型均出现基因突变，且突变模式相似。最后，研究依据cMAP数据库识别出一些可能靶向两亚型间DEG的小分子，如epibatidine、mepyramine和reboxetine。
总之，研究发现KIRC不同亚型患者的生存结局、对免疫微环境的敏感性及免疫治疗应答均有所不同。这些发现有助于未来进一步开展KIRC机制研究和治疗探索。
展开英文摘要原文
Previous studies have revealed the essential role of lysosomes in human diseases, including cancer.
However, there is a lack of in-depth systematic research on its function in kidney renal clear cell carcinoma (KIRC). In this project, we collected the public dataset of KIRC and selected lysosomal genes tightly linked with survival. Cluster analysis uncovered that these genes possess good classification ability and can divide KIRC patients into multiple subtypes with different survival rates. Enrichment analyses revealed that the main biological processes associated with differentially expressed genes (DEGs) in the two representative subpopulations with the largest survival differences (cluster1 and cluster2) were steroid metabolic process, neutrophil extracellular trap formation, and tyrosine metabolism.
The immune-related analysis demonstrated notable differences in immune cell infiltration levels between cluster1 and cluster2 subpopulations of KIRC. More specifically, Tfh and TIL were highly infiltrated in the cluster1, and Type II IFN response, mast cells, and basophils were highly infiltrated in the cluster2.
The immunotherapy-related analysis demonstrated that cluster1 may be more sensitive to immunotherapy and more likely to benefit from immunotherapy due to its higher immune checkpoint expression, ESTIMATE score, immune score, and higher immunophenoscore (IPS).
In addition, gene mutations occurred in the two subtypes, exhibiting similar mutation patterns between the two subtypes.
Finally, based on the cMAP database, we identified some small molecules that may target DEGs between the two subtypes, such as epibatidine, mepyramine, and reboxetine.
In conclusion, our investigation unearthed that different subtypes of KIRC patients exhibited different survival outcomes and sensitivity to the immune microenvironment, as well as different responses to immunotherapy.
These findings may be beneficial for further mechanistic exploration and therapeutic research of KIRC in the future.
论文信息
- 作者
- Jin Y、Zhang Q、Wang F、Wu Y、Guo X
- 第一作者单位
- Department of Urology, Jiaxing Second Hospital, Jiaxing 314000, China.China
- 通讯作者单位
- Department of Urology, Jiaxing Second Hospital, Jiaxing 314000, China. Electronic address: Xiao_Guo33@163.com.China
- 期刊
- Human immunology2025 Jan
- 原文标识
- PubMed 39755002 · DOI 10.1016/j.humimm.2024.111223