Pan Yan, Wang Yingjian, Hu Mengsi, Xu Shoufang, Jiang Feiyu, Han Yetao, Chen Fangjian, Liu Zhiwei
Department of Blood Transfusion, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
Department of Blood Transfusion, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Front Oncol. 2023 Jul 17;13:1195392. doi: 10.3389/fonc.2023.1195392. eCollection 2023.
Acute myeloid leukemia (AML) is a complex mixed entity composed of malignant tumor cells, immune cells and stromal cells, with intra-tumor and inter-tumor heterogeneity. Single-cell RNA sequencing enables a comprehensive study of the highly complex tumor microenvironment, which is conducive to exploring the evolutionary trajectory of tumor cells. Herein, we carried out comprehensive analyses of aggrephagy-related cell clusters based on single-cell sequencing for patients with acute myeloid leukemia. A total of 11 specific cell types (T, NK, CMP, Myeloid, GMP, MEP, Promono, Plasma, HSC, B, and Erythroid cells) using t-SNE dimension reduction analysis. Several aggrephagy-related genes were highly expressed in the 11 specific cell types. Using Monocle analysis and NMF clustering analysis, six aggrephagy-related CD8 T clusters, six aggrephagy-related NK clusters, and six aggrephagy-related Mac clusters were identified. We also evaluated the ligand-receptor links and Cell-cell communication using CellChat package and CellChatDB database. Furthermore, the transcription factors (TFs) of aggrephagy-mediated cell clusters for AML were assessed through pySCENIC package. Prognostic analysis of the aggrephagy-related cell clusters based on R package revealed the differences in prognosis of aggrephagy-mediated cell clusters. Immunotherapy of the aggrephagy-related cell clusters was investigated using TIDE algorithm and public immunotherapy cohorts. Our study revealed the significance of aggrephagy-related patterns in tumor microenvironment, prognosis, and immunotherapy for AML.
急性髓系白血病（AML）是一种由恶性肿瘤细胞、免疫细胞和基质细胞组成的复杂混合实体，具有肿瘤内和肿瘤间的异质性。单细胞RNA测序能够全面研究高度复杂的肿瘤微环境，这有助于探索肿瘤细胞的进化轨迹。在此，我们基于单细胞测序对急性髓系白血病患者的自噬相关细胞簇进行了综合分析。使用t-SNE降维分析共鉴定出11种特定细胞类型（T细胞、自然杀伤细胞、粒-单核祖细胞、髓系细胞、粒-巨噬细胞祖细胞、巨核细胞-红细胞祖细胞、原单核细胞、浆细胞、造血干细胞、B细胞和红细胞）。几个自噬相关基因在这11种特定细胞类型中高表达。使用Monocle分析和非负矩阵分解（NMF）聚类分析，鉴定出6个自噬相关的CD8 T细胞簇、6个自噬相关的自然杀伤细胞簇和6个自噬相关的巨噬细胞簇。我们还使用CellChat软件包和CellChatDB数据库评估了配体-受体联系和细胞间通讯。此外，通过pySCENIC软件包评估了AML自噬介导细胞簇的转录因子。基于R软件包对自噬相关细胞簇进行预后分析，揭示了自噬介导细胞簇预后的差异。使用TIDE算法和公共免疫治疗队列研究了自噬相关细胞簇的免疫治疗。我们的研究揭示了自噬相关模式在AML肿瘤微环境、预后和免疫治疗中的重要性。
