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构建铁死亡相关基因特征,以鉴定骨关节炎中的潜在生物标志物和免疫细胞浸润。

Construction of ferroptosis-related gene signatures for identifying potential biomarkers and immune cell infiltration in osteoarthritis.

机构信息

Department of Clinical Laboratory, Zhengzhou Orthopaedics Hospital, Zhengzhou, People's Republic of China.

Department of Clinical Laboratory, Henan University Orthopedic Hospital, Zhengzhou, People's Republic of China.

出版信息

Artif Cells Nanomed Biotechnol. 2024 Dec;52(1):449-461. doi: 10.1080/21691401.2024.2402298. Epub 2024 Sep 11.

Abstract

Osteoarthritis (OA) is a comprehensive joint disorder. The specific genes that trigger OA and the strategies for its effective management are not fully understood. This study focuses on identifying key genes linked to iron metabolism that could influence both the diagnosis and therapeutic approaches for OA. Analysis of GEO microarray data and iron metabolism genes identified 15 ferroptosis-related DEGs, enriched in hypoxia and HIF-1 pathways. Ten key hub genes (, , , , , , , , , ) were identified. Through stepwise regression, we screened 4 out of the above 10 genes, namely, , , , and , to obtain the optimal model. AUROCs for diagnosis of OA for the four hub genes were 0.81 and 0.80 of training and validation sets, separately. According to immune infiltration results, OA was related to significantly increased memory B cells, M0 macrophages, regulatory T cells, and resting mast cells but decreased activated dendritic cells. The four hub genes showed a close relation to them. It is anticipated that this model will aid in diagnosing osteoarthritis by assessing the expression of specific genes in blood samples. Moreover, studying these hub genes may further elucidate the pathogenesis of osteoarthritis.

摘要

骨关节炎(OA)是一种综合性关节疾病。引发 OA 的特定基因以及其有效管理策略尚未完全了解。本研究专注于确定与铁代谢相关的关键基因,这些基因可能会影响 OA 的诊断和治疗方法。通过对 GEO 微阵列数据和铁代谢基因的分析,确定了 15 个与铁死亡相关的差异表达基因,这些基因富集在缺氧和 HIF-1 途径中。确定了 10 个关键的枢纽基因(、、、、、、、、、)。通过逐步回归,我们筛选出了上述 10 个基因中的 4 个,即、、、和,以获得最佳模型。四个枢纽基因在训练集和验证集中诊断 OA 的 AUROC 分别为 0.81 和 0.80。根据免疫浸润结果,OA 与记忆 B 细胞、M0 巨噬细胞、调节性 T 细胞和静止肥大细胞的显著增加有关,但与激活的树突状细胞的减少有关。这四个枢纽基因与它们密切相关。预计该模型将通过评估血液样本中特定基因的表达来帮助诊断骨关节炎。此外,研究这些枢纽基因可能会进一步阐明骨关节炎的发病机制。

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