Aggrephagy-related patterns in tumor microenvironment, prognosis, and immunotherapy for acute myeloid leukemia: a comprehensive single-cell RNA sequencing analysis

Yan Pan; Yingjian Wang; Mengsi Hu; Shoufang Xu; Feiyu Jiang; Yetao Han; Fangjian Chen; Zhiwei Liu

doi:10.3389/fonc.2023.1195392

Aggrephagy-related patterns in tumor microenvironment, prognosis, and immunotherapy for acute myeloid leukemia: a comprehensive single-cell RNA sequencing analysis

Front Oncol. 2023 Jul 17:13:1195392. doi: 10.3389/fonc.2023.1195392. eCollection 2023.

Authors

Yan Pan¹, Yingjian Wang², Mengsi Hu², Shoufang Xu², Feiyu Jiang², Yetao Han², Fangjian Chen¹, Zhiwei Liu²

Affiliations

¹ Department of Blood Transfusion, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
² Department of Blood Transfusion, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Abstract

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.

Keywords: acute myeloid leukemia; aggrephagy; immune cell; immunotherapy; microenvironment; prognosis.

Grants and funding

This study was supported by grants from Zhejiang Traditional Chinese Medicine Science and Technology Project (ZYJ23JS03), Natural Science Foundation of Zhejiang Province (LGF22H080009) and Guiding Science and Technology Project of Quzhou (2022014).