Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China.
Folia Biol (Praha). 2024;70(2):85-94. doi: 10.14712/fb2024070020085.
Lysosomes are crucial in the tumour immune microenvironment, which is essential for the survival and homeostasis in multiple myeloma (MM). Here, we aimed to identify lysosome-related genes for the prognosis of MM and predicted their regulatory mechanisms. Gene expression profiles of MM from the GSE2658 and GSE57317 datasets were analysed. Lysosome-related differentially expressed genes (DEGs) were identified and used for molecular subtyping of MM patients. A prognostic model was constructed using univariate Cox regression and LASSO regression analyses. The relationship between prognostic genes, immune cell types, and autophagy pathways was assessed through correlation analysis. RT-qPCR was performed to validate the expression of prognostic genes in MM cells. A total of 9,954 DEGs were identified between high and low immune score groups, with 213 intersecting with lysosomal genes. Molecular subtyping revealed two distinct MM subtypes with significant differences in immune cell types and autophagy pathway activities. Five lysosome-related DEGs (CORO1A, ELANE, PSAP, RNASE2, and SNAPIN) were identified as significant prognostic markers. The prognostic model showed moderate predictive accuracy with AUC values up to 0.723. Prognostic genes demonstrated significant correlations with various immune cell types and autophagy pathways. Additionally, CORO1A, PSAP and RNASE2 expression was up-regulated in MM cells, while ELANE and SNAPIN were down-regulated. Five lysosomal genes in MM were identified, and a new risk model for prognosis was developed using these genes. This research could lead to discovering important gene markers for the treatment and prognosis of MM.
溶酶体在肿瘤免疫微环境中至关重要，这对于多发性骨髓瘤（MM）的存活和体内平衡至关重要。在这里，我们旨在鉴定与 MM 预后相关的溶酶体相关基因，并预测其调控机制。分析了来自 GSE2658 和 GSE57317 数据集的 MM 的基因表达谱。鉴定了与溶酶体相关的差异表达基因（DEG），并用于 MM 患者的分子亚分型。使用单变量 Cox 回归和 LASSO 回归分析构建了预后模型。通过相关性分析评估了预后基因与免疫细胞类型和自噬途径的关系。通过 RT-qPCR 验证了 MM 细胞中预后基因的表达。在高免疫评分组和低免疫评分组之间鉴定了 9954 个 DEG，其中 213 个与溶酶体基因重叠。分子亚分型显示两种不同的 MM 亚型，免疫细胞类型和自噬途径活性存在显著差异。鉴定了 5 个与溶酶体相关的 DEG（CORO1A、ELANE、PSAP、RNASE2 和 SNAPIN）作为显著的预后标志物。预后模型具有中等的预测准确性，AUC 值高达 0.723。预后基因与各种免疫细胞类型和自噬途径表现出显著的相关性。此外，CORO1A、PSAP 和 RNASE2 在 MM 细胞中表达上调，而 ELANE 和 SNAPIN 表达下调。在 MM 中鉴定了 5 个溶酶体基因，并使用这些基因开发了新的预后风险模型。这项研究可能会发现用于 MM 治疗和预后的重要基因标志物。
