Ferroptosis-related genes LPCAT3 and PGD are potential diagnostic biomarkers for osteoarthritis.
Ferroptosis-related genes LPCAT3 and PGD are potential diagnostic biomarkers for osteoarthritis.
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DOI：
10.1186/s13018-023-04128-2
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发表时间：
2023-09-19
影响因子：
2.6
通讯作者：
Fang, Jie
中科院分区：
文献类型：
--
作者：
Wang, Lufei;Ye, Shouxiu;Qin, Jianliang;Tang, Min;Dong, Ming-You;Fang, Jie
骨关节炎（OA）是最常见的慢性关节疾病，近年来铁缺乏症在OA中的作用引起了广泛关注。生物信息学促进了骨关节炎铁中毒相关生物标志物的发现。但由于OA是一种全关节疾病，OA的敏感生物标志物仍然有限。在此，我们专注于软骨下骨，一个经常被现有生物信息学报告忽视的关节成分，以确定骨关节炎的铁蛋白沉积相关诊断生物标志物。微阵列数据集GSE 51588和GSE 55457从Gene Expression Omnibus数据库下载。鉴定骨关节炎和正常骨组织中与铁中毒相关的差异表达基因（Fer-DEG），并分析其功能富集情况。使用SVM-RFE、LASSO回归和RandomForest机器学习算法的组合从Ferr-DEG中选择用于OA诊断的常见基因。用受试者工作特征曲线（ROC）验证共同基因的诊断价值，用CIBERSORT分析共同基因与免疫浸润的关系。最后，通过RT-PCR方法验证候选基因在骨关节炎患者软骨细胞和体外IL-1β诱导的骨关节炎模型中的表达。两个铁中毒相关基因LPCAT 3和PGD被确定为OA诊断的生物标志物，并通过ROC诊断测试证实。LPCAT 3和PGD与几种类型的免疫细胞的浸润的关联被鉴定。在OA软骨细胞和IL-1β诱导的OA条件下均证实了LPCAT 3和PGD的表达降低。我们确定了铁凋亡相关基因LPCAT 3和PGD作为OA的潜在诊断生物标志物，这可能有助于深入了解铁凋亡在OA中的作用，并为OA的诊断和治疗提供有用的信息。
Osteoarthritis (OA) is the most common chronic joint disease and how ferroptosis contributes to OA has garnered much attention recently. Bioinformatics promoted the discovery of ferroptosis-related biomarkers for OA. But since OA is a whole-joint disease, sensitive biomarkers for OA are still limited. We herein focused on subchondral bone, a joint component often-ignored by existing bioinformatic reports, to identify ferroptosis-related diagnostic biomarkers for OA. Microarray datasets GSE51588 and GSE55457 were downloaded from Gene Expression Omnibus database. Ferroptosis-related differential expression genes (Ferr-DEGs) between OA and normal samples were identified and their functional enrichment was analyzed. Common genes for OA diagnosis were selected from Ferr-DEGs using the combination of SVM-RFE, LASSO regression, and RandomForest machine learning algorithms. Common genes' diagnostic value was verified by receiver operating characteristic (ROC) curve and their association with immune infiltration was analyzed by CIBERSORT. Finally, candidate gene’s expression was verified in chondrocytes from OA patients and in an in vitro IL-1β-induced OA model, by RT-PCR. Two ferroptosis-related genes, LPCAT3 and PGD, were identified as OA diagnostic biomarkers and confirmed by ROC diagnostic test. The association of LPCAT3 and PGD with the infiltration of several types of immune cells was identified. The decreased expression of LPCAT3 and PGD was both confirmed in OA chondrocytes and IL-1β-induced OA condition. We identified ferroptosis-related genes LPCAT3 and PGD as potential diagnostic biomarkers for OA, which may offer insight into the role of ferroptosis in OA and provides useful information for the diagnosis and treatment of OA.
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影响因子：
14.8
作者：
Kagan VE;Mao G;Qu F;Angeli JP;Doll S;Croix CS;Dar HH;Liu B;Tyurin VA;Ritov VB;Kapralov AA;Amoscato AA;Jiang J;Anthonymuthu T;Mohammadyani D;Yang Q;Proneth B;Klein-Seetharaman J;Watkins S;Bahar I;Greenberger J;Mallampalli RK;Stockwell BR;Tyurina YY;Conrad M;Bayır H
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Stockwell BR
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