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股骨头坏死的脂质组学分析及生物标志物鉴定研究

Research on Lipidomic Profiling and Biomarker Identification for Osteonecrosis of the Femoral Head.

作者信息

Yan Yuzhu, Wang Jihan, Wang Yangyang, Wu Wenjing, Chen Wei

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

Clinical Laboratory of Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, China.

出版信息

Biomedicines. 2024 Dec 12;12(12):2827. doi: 10.3390/biomedicines12122827.

Abstract

Abnormal lipid metabolism is increasingly recognized as a contributing factor to the development of osteonecrosis of the femoral head (ONFH). This study aimed to explore the lipidomic profiles of ONFH patients, focusing on distinguishing between traumatic ONFH (TONFH) and non-traumatic ONFH (NONFH) subtypes and identifying potential biomarkers for diagnosis and understanding pathogenesis. Plasma samples were collected from 92 ONFH patients (divided into TONFH and NONFH subtypes) and 33 healthy normal control (NC) participants. Lipidomic profiling was performed using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Data analysis incorporated a machine learning-based feature selection method, least absolute shrinkage and selection operator (LASSO) regression, to identify significant lipid biomarkers. Distinct lipidomic signatures were observed in both TONFH and NONFH groups compared to the NC group. LASSO regression identified 11 common lipid biomarkers that signify shared metabolic disruptions in both ONFH subtypes, several of which exhibited strong diagnostic performance with areas under the curve (AUCs) > 0.7. Additionally, subtype-specific lipid markers unique to TONFH and NONFH were identified, providing insights into the differential pathophysiological mechanisms underlying these subtypes. This study highlights the importance of lipidomic profiling in understanding ONFH-associated metabolic disorders and demonstrates the utility of machine learning approaches, such as LASSO regression, in high-dimensional data analysis. These findings not only improve disease characterization but also facilitate the discovery of diagnostic and mechanistic biomarkers, paving the way for more personalized therapeutic strategies in ONFH.

摘要

脂质代谢异常日益被认为是股骨头坏死(ONFH)发展的一个促成因素。本研究旨在探索ONFH患者的脂质组学特征,重点区分创伤性ONFH(TONFH)和非创伤性ONFH(NONFH)亚型,并识别用于诊断和理解发病机制的潜在生物标志物。从92例ONFH患者(分为TONFH和NONFH亚型)和33名健康正常对照(NC)参与者中采集血浆样本。使用超高效液相色谱-串联质谱(UHPLC-MS/MS)进行脂质组学分析。数据分析采用基于机器学习的特征选择方法,即最小绝对收缩和选择算子(LASSO)回归,以识别显著的脂质生物标志物。与NC组相比,在TONFH和NONFH组中均观察到明显的脂质组学特征。LASSO回归确定了11种常见的脂质生物标志物,这些标志物表明两种ONFH亚型存在共同的代谢紊乱,其中几种在曲线下面积(AUC)>0.7时表现出很强的诊断性能。此外,还确定了TONFH和NONFH特有的亚型特异性脂质标志物,为了解这些亚型潜在的不同病理生理机制提供了线索。本研究强调了脂质组学分析在理解ONFH相关代谢紊乱中的重要性,并证明了机器学习方法(如LASSO回归)在高维数据分析中的实用性。这些发现不仅改善了疾病特征描述,还促进了诊断和机制生物标志物的发现,为ONFH更个性化的治疗策略铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e9b/11673004/27e1db27f451/biomedicines-12-02827-g001.jpg

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