Constructing a ferroptosis-related prognostic model for osteosarcoma based on scRNA-seq dataset and WGCNA analysis.

IF 0.9 Q4 ONCOLOGY
International journal of clinical and experimental pathology Pub Date : 2025-07-15 eCollection Date: 2025-01-01 DOI:10.62347/QVON7675
Hong-Chi Yi, Qing-Zhong Wei, Ji-Ming Gan, Jia-Jia Wei, Jian-Qing Liao, Dun Liu, Zhuo-Qian Dong, Xi-Hua Zhang, Zhong-Yu Peng, Tao Chen, Bao-Chuang Qi
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引用次数: 0

Abstract

Osteosarcoma (OS) is a primary malignant bone tumor. Ferroptosis is closely related to the progression of osteosarcoma. The aim of this study is to explore the mechanism of ferroptosis-related genes in the progression of osteosarcoma.

Methods: Utilizing the scRNA-seq dataset of osteosarcoma, differentially expressed genes (scRNA-DEGs) were identified between the osteosarcoma group and the control group, and ferroptosis-related genes in the TARGET-OS dataset were identified through WGCNA. By intersecting these two sets of ferroptosis-related genes, key candidate genes related to ferroptosis were obtained. The prognostic genes were selected from key candidate genes through univariate Cox and LASSO regression analysis. A prognostic model based on these genes was then constructed to investigate the relationship between ferroptosis and the prognosis of osteosarcoma patients. The correlation between the prognostic genes and immune cells, as well as immune checkpoint genes, was investigated through immune infiltration analysis. The drugs binding to prognostic genes were predicted.

Results: We identified 48 ferroptosis-related genes in the scRNA-seq dataset, and 3859 ferroptosis-related genes were identified in the TARGET-OS dataset. After intersecting the two sets, 12 key ferroptosis-related genes were obtained, among which four genes (IFNG, HMOX1, CDKN1A, LGMN) were related to the prognosis of osteosarcoma patients. The prognostic model could accurately predict patient survival with good stability. Immune infiltration analysis revealed that the prognostic genes were significantly correlated with multiple immune cell types, and the expression of some immune checkpoint genes showed significant differences between control and osteosarcoma groups. Furthermore, we found that the prognostic genes were highly expressed in osteoblasts and macrophages.

Conclusions: Four genes (IFNG, HMOX1, CDKN1A, LGMN) were closely related to the prognosis of osteosarcoma patients. These genes may serve as potential therapeutic targets for the treatment of osteosarcoma.

基于scRNA-seq数据集和WGCNA分析构建骨肉瘤凋亡相关预后模型。
骨肉瘤是一种原发性骨恶性肿瘤。铁下垂与骨肉瘤的发展密切相关。本研究旨在探讨嗜铁相关基因在骨肉瘤发生发展中的作用机制。方法:利用骨肉瘤scRNA-seq数据集,鉴定骨肉瘤组与对照组之间的差异表达基因(scRNA-DEGs),并通过WGCNA鉴定TARGET-OS数据集中的嗜铁相关基因。通过交叉这两组与铁下垂相关的基因,获得了与铁下垂相关的关键候选基因。通过单因素Cox和LASSO回归分析,从关键候选基因中筛选出影响预后的基因。然后构建基于这些基因的预后模型来研究铁下垂与骨肉瘤患者预后的关系。通过免疫浸润分析,探讨预后基因与免疫细胞及免疫检查点基因的相关性。预测与预后基因结合的药物。结果:我们在scRNA-seq数据集中鉴定了48个与铁衰相关的基因,在TARGET-OS数据集中鉴定了3859个与铁衰相关的基因。两组交叉后得到12个关键的嗜铁相关基因,其中IFNG、HMOX1、CDKN1A、LGMN 4个基因与骨肉瘤患者的预后相关。该预后模型能准确预测患者生存,且稳定性好。免疫浸润分析显示,预后基因与多种免疫细胞类型显著相关,部分免疫检查点基因的表达在对照组和骨肉瘤组之间存在显著差异。此外,我们发现预后基因在成骨细胞和巨噬细胞中高度表达。结论:IFNG、HMOX1、CDKN1A、LGMN四个基因与骨肉瘤患者的预后密切相关。这些基因可能成为骨肉瘤治疗的潜在靶点。
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来源期刊
自引率
0.00%
发文量
42
审稿时长
1 months
期刊介绍: The International Journal of Clinical and Experimental Pathology (IJCEP, ISSN 1936-2625) is a peer reviewed, open access online journal. It was founded in 2008 by an international group of academic pathologists and scientists who are devoted to the scientific exploration of human disease and the rapid dissemination of original data. Unlike most other open access online journals, IJCEP will keep all the traditional features of paper print that we are all familiar with, such as continuous volume and issue numbers, as well as continuous page numbers to keep our warm feelings towards an academic journal. Unlike most other open access online journals, IJCEP will keep all the traditional features of paper print that we are all familiar with, such as continuous volume and issue numbers, as well as continuous page numbers to keep our warm feelings towards an academic journal.
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