单细胞测序揭示了聚集自噬信号与多发性骨髓瘤免疫微环境组成的相关性。

Single-cell sequencing reveals the correlation of aggrephagy signaling and multiple myeloma immune microenvironment composition.

机构信息

Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.

Department of Hematology, The Affiliated Hospital of Chengdu University, Chengdu, China.

出版信息

J Gene Med. 2024 Jul;26(7):e3712. doi: 10.1002/jgm.3712.

DOI:10.1002/jgm.3712

PMID:38949072

Abstract

Aggrephagy, a type of autophagy, degrades the aggregation of misfolded protein in cells. However, the role of aggrephagy in multiple myeloma (MM) has not been fully demonstrated. In this study, we first investigated the correlation between aggrephagy signaling, MM immune microenvironment composition and disease prognosis. Single-cell RNA-seq data, including the expression profiles of 12,187 single cells from seven MM bone marrow (BM) and seven healthy BM samples, were analyzed by non-negative matrix factorization for 44 aggrephagy-related genes. Bulk RNA-seq cohorts from the Gene Expression Omnibus database were used to evaluate the prognostic value of aggrephagy-related immune cell subtypes and predict immune checkpoint blockade immunotherapeutic response in MM. Compared with healthy BM, MM BM exhibited different patterns of aggrephagy-related gene expression. In MM BM, macrophages, CD8 T cells, B cells and natural killer cells could be grouped into four to nine aggrephagy-related subclusters. The signature of aggrephagy signaling molecule expression in the immune cells correlates with the patient's prognosis. Our investigation provides a novel view of aggrephagy signaling in MM tumor microenvironment cells, which might be a prognostic indicator and potential target for MM treatment.

摘要

聚集体自噬是一种自噬，可降解细胞中错误折叠蛋白的聚集物。然而，聚集体自噬在多发性骨髓瘤（MM）中的作用尚未得到充分证实。在这项研究中，我们首先研究了聚集体自噬信号与 MM 免疫微环境组成和疾病预后之间的相关性。通过非负矩阵分解分析了来自七个 MM 骨髓（BM）和七个健康 BM 样本的 12187 个单细胞的单细胞 RNA-seq 数据，以研究 44 个与聚集体自噬相关的基因。使用来自基因表达综合数据库的批量 RNA-seq 队列来评估与聚集体自噬相关的免疫细胞亚型的预后价值，并预测 MM 中免疫检查点阻断免疫治疗反应。与健康 BM 相比，MM BM 表现出不同的与聚集体自噬相关基因表达模式。在 MM BM 中，巨噬细胞、CD8 T 细胞、B 细胞和自然杀伤细胞可分为四个到九个与聚集体自噬相关的亚群。免疫细胞中聚集体自噬信号分子表达的特征与患者的预后相关。我们的研究为 MM 肿瘤微环境细胞中的聚集体自噬信号提供了新的视角，它可能是 MM 治疗的预后指标和潜在靶点。