Construction of regulatory network for alopecia areata progression and identification of immune monitoring genes based on multiple machine-learning algorithms.
Jiachao Xiong, Guodong Chen, Zhixiao Liu, Xuemei Wu, Sha Xu, Jun Xiong, Shizhao Ji, Minjuan Wu
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引用次数: 1
Abstract
Objectives: Alopecia areata (AA) is an autoimmune-related non-cicatricial alopecia, with complete alopecia (AT) or generalized alopecia (AU) as severe forms of AA. However, there are limitations in early identification of AA, and intervention of AA patients who may progress to severe AA will help to improve the incidence rate and prognosis of severe AA.
Methods: We obtained two AA-related datasets from the gene expression omnibus database, identified the differentially expressed genes (DEGs), and identified the module genes most related to severe AA through weighted gene co-expression network analysis. Functional enrichment analysis, construction of a protein-protein interaction network and competing endogenous RNA network, and immune cell infiltration analysis were performed to clarify the underlying biological mechanisms of severe AA. Subsequently, pivotal immune monitoring genes (IMGs) were screened through multiple machine-learning algorithms, and the diagnostic effectiveness of the pivotal IMGs was validated by receiver operating characteristic.
Results: A total of 150 severe AA-related DEGs were identified; the upregulated DEGs were mainly enriched in immune response, while the downregulated DEGs were mainly enriched in pathways related to hair cycle and skin development. Four IMGs (LGR5, SHISA2, HOXC13, and S100A3) with good diagnostic efficiency were obtained. As an important gene of hair follicle stem cells stemness, we verified in vivo that LGR5 downregulation may be an important link leading to severe AA.
Conclusion: Our findings provide a comprehensive understanding of the pathogenesis and underlying biological processes in patients with AA, and identification of four potential IMGs, which is helpful for the early diagnosis of severe AA.
期刊介绍:
Precision Clinical Medicine (PCM) is an international, peer-reviewed, open access journal that provides timely publication of original research articles, case reports, reviews, editorials, and perspectives across the spectrum of precision medicine. The journal's mission is to deliver new theories, methods, and evidence that enhance disease diagnosis, treatment, prevention, and prognosis, thereby establishing a vital communication platform for clinicians and researchers that has the potential to transform medical practice. PCM encompasses all facets of precision medicine, which involves personalized approaches to diagnosis, treatment, and prevention, tailored to individual patients or patient subgroups based on their unique genetic, phenotypic, or psychosocial profiles. The clinical conditions addressed by the journal include a wide range of areas such as cancer, infectious diseases, inherited diseases, complex diseases, and rare diseases.