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利用机器学习识别银屑病潜在的铁死亡生物标志物并分析免疫细胞浸润

Identification of Potential Ferroptosis Biomarkers and Analysis of Immune Cell Infiltration in Psoriasis Using Machine Learning.

作者信息

Wu Xiaoyan, Sun Yuzhe, Wei Shuyi, Hu Huoyou, Yang Bin

机构信息

Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People's Republic of China.

Department of Dermatology, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, People's Republic of China.

出版信息

Clin Cosmet Investig Dermatol. 2024 May 31;17:1281-1295. doi: 10.2147/CCID.S457958. eCollection 2024.

Abstract

BACKGROUND

Ferroptosis is a type of cell death characterized by the accumulation of iron-dependent lethal lipid peroxides, which is associated with various pathophysiological processes. Psoriasis is a chronic autoimmune skin disease accompanied by abnormal immune cell infiltration and excessive production of lipid reactive oxygen species (ROS). Currently, its pathogenesis remains elusive, especially the potential role of ferroptosis in its pathophysiological process.

METHODS

The microarrays GSE13355 (58 psoriatic skin specimens versus 122 healthy skin specimens) and the ferroptosis database were employed to identify the common differentially expressed genes (DEGs) associated with psoriasis and ferroptosis. The functions of common DEGs were investigated through functional enrichment analysis and protein-protein interaction analysis. The potential diagnostic markers for psoriasis among the common DEGs were identified using four machine-learning algorithms. DGIdb was utilized to explore potential therapeutic agents for psoriasis. Additionally, CIBERSORT was employed to investigate immune infiltration in psoriasis.

RESULTS

A total of 8 common DEGs associated with psoriasis and ferroptosis were identified, which are involved in intercellular signaling and affect pathways of cell response to stress and stimulation. Four machine-learning algorithms were employed to identify poly (ADP-ribose) polymerase 12 (PARP12), frizzled homolog 7 (FZD7), and arachidonate 15-lipoxygenase (ALOX15B) among the eight common DEGs as potential diagnostic markers for psoriasis. A total of 18 drugs targeting the five common DEGs were identified as potential candidates for treating psoriasis. Additionally, significant changes were observed in the immune microenvironment of patients with psoriasis.

CONCLUSION

This study has contributed to our enhanced comprehension of ferroptosis-related genes as potential biomarkers for psoriasis diagnosis, as well as the alterations in the immune microenvironment associated with psoriasis. Our findings offer valuable insights into the diagnosis and treatment of psoriasis.

摘要

背景

铁死亡是一种细胞死亡类型,其特征是铁依赖性致死性脂质过氧化物的积累,这与多种病理生理过程相关。银屑病是一种慢性自身免疫性皮肤病,伴有异常免疫细胞浸润和脂质活性氧(ROS)的过度产生。目前,其发病机制仍不清楚,尤其是铁死亡在其病理生理过程中的潜在作用。

方法

使用微阵列GSE13355(58例银屑病皮肤标本与122例健康皮肤标本)和铁死亡数据库来鉴定与银屑病和铁死亡相关的共同差异表达基因(DEGs)。通过功能富集分析和蛋白质-蛋白质相互作用分析来研究共同DEGs的功能。使用四种机器学习算法在共同DEGs中鉴定银屑病的潜在诊断标志物。利用DGIdb探索银屑病的潜在治疗药物。此外,采用CIBERSORT研究银屑病中的免疫浸润情况。

结果

共鉴定出8个与银屑病和铁死亡相关的共同DEGs,它们参与细胞间信号传导,并影响细胞对应激和刺激的反应途径。采用四种机器学习算法在这8个共同DEGs中鉴定出聚(ADP-核糖)聚合酶12(PARP12)、卷曲同源物7(FZD7)和花生四烯酸15-脂氧合酶(ALOX15B)作为银屑病的潜在诊断标志物。共鉴定出18种靶向这5个共同DEGs的药物作为治疗银屑病的潜在候选药物。此外,观察到银屑病患者免疫微环境有显著变化。

结论

本研究有助于我们更好地理解与铁死亡相关的基因作为银屑病诊断潜在生物标志物的作用,以及与银屑病相关的免疫微环境变化。我们的发现为银屑病的诊断和治疗提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78d7/11149635/6b16f27a9bfa/CCID-17-1281-g0001.jpg

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