| 摘要: |
| 目的 基于单细胞测序数据对肝细胞癌（HCC）铁死亡相关预后基因的表达状态进行分析，为HCC的精准治疗提供有效靶点。方法 利用癌症基因组图谱（TCGA）数据库和铁死亡相关基因数据库获取HCC患者和正常组织样本的铁死亡相关差异基因，采用最小绝对收缩和选择算子（LASSO）回归分析构建风险预后评估模型；利用单细胞测序数据，通过t-分布随机近邻嵌入（tSNE）聚类降维和Monocle包对预后风险基因在不同发育阶段细胞中的表达情况进行分析，并进一步通过CellChat包对预后风险基因在HCC细胞间的相互作用进行分析。结果 共发现25个铁死亡相关差异基因与HCC患者的预后相关。筛选出含5'-核苷酸酶结构域2（NT5DC2）、葡萄糖-6-磷酸脱氢酶（G6PD）、微管解聚蛋白1（STMN1）和白细胞介素（IL）33（IL-33）4个基因作为HCC预后基因。其中NT5DC2主要在上皮细胞和内皮细胞中表达，IL-33主要在内皮细胞中表达，G6PD和STMN1在细胞中广泛表达；IL-33主要在发育早期阶段的内皮细胞中表达，NT5DC2、G6PD、STMN在不同的发育阶段均有表达；此外IL-33只在发育早期阶段的内皮细胞中与受体存在广泛交互。结论 IL-33作为良性预后基因，在HCC患者发育早期阶段的内皮细胞中特异性表达并发挥作用，提示维持血管内皮细胞的这种原始状态或促进IL-33介导的原始状态内皮细胞铁死亡可能是有效的HCC治疗靶点。 |
| 关键词: 肝细胞癌 预后 铁死亡 单细胞测序 拟时序分析 细胞互作分析 白细胞介素33 |
| DOI：10.16781/j.CN31-2187/R.20230148 |
| 投稿时间：2023-03-29修订日期：2023-04-23 |
| 基金项目:国家重点研发计划（2018YFA010830），国家自然科学基金（82273317）. |
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| Role of ferroptosis-related differentially expressed gene interleukin 33 in endothelial cells at early stage of hepatocellular carcinoma based on single cell sequencing data |
| LUO Shudan1,WANG Duoxiang2,FU Ruifeng2,WANG Ling2,WANG Tengjiao2*,WANG Yue2* |
(1. College of Basic Medical Sciences, Naval Medical University(Second Military Medical University), Shanghai 200433, China;
2. Laboratory of Stem Cell and Regenerative Medicine, Center of Translational Medicine, Naval Medical University(Second Military Medical University), Shanghai 200433, China
*Corresponding authors) |
| Abstract: |
| Objective To analyze the expression of ferroptosis-related prognostic genes in hepatocellular carcinoma (HCC) based on single cell sequencing data, so as to provide effective targets for precise treatment of HCC. Methods The Cancer Genome Atlas (TCGA) database and ferroptosis-related gene database were used to obtain ferroptosis-related differentially expressed genes in HCC patients and normal tissue samples, and least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct risk prognosis assessment model. Using single cell sequencing data, we analyzed the expression of prognostic risk genes in HCC cells at different developmental stages by t-distributed stochastic neighbor embedding (tSNE) dimensionality reduction and Monocle package, and the interactions between prognostic risk genes in HCC cells were further analyzed by CellChat package. Results A total of 25 ferroptosis-related differentially expressed genes were found to be associated with the prognosis of HCC patients. And 5'-nucleotidase domain containing 2 (NT5DC2), glucose-6-phosphate dehydrogenase (G6PD), stathmin1 (STMN1) and interleukin 33 (IL-33) were selected as HCC prognostic genes. Among them, NT5DC2 was mainly expressed in epithelial and endothelial cells, IL-33 was mainly expressed in endothelial cells, and G6PD and STMN1 were widely expressed in cells. IL-33 was mainly expressed in endothelial cells at early developmental stages, while NT5DC2, G6PD and STMN were expressed at different developmental stages. Moreover, IL-33 interacted extensively with its receptor only in endothelial cells at early stage of development. Conclusion As a benign prognostic gene, IL-33 is specifically expressed and plays a role in endothelial cells at the early stage of HCC development, suggesting that maintaining this primitive state of vascular endothelial cells or promoting IL-33-mediated primitive endothelial ferroptosis may be an effective therapeutic target for HCC. |
| Key words: hepatocellular carcinoma prognosis ferroptosis single cell sequencing pseudotime analysis cell interaction analysis interleukin 33 |
