Transcriptome Analysis Reveals a Two-Gene Signature Links to Motor Progression and Alterations of Immune Cells in Parkinson's Disease

转录组分析揭示双基因标记与帕金森病的运动进展和免疫细胞改变相关

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作者:Weimin Li, Jiaqi Shen, Hao Wu, Lishan Lin, Yanmei Liu, Zhong Pei, Ganqiang Liu

Background

The motor impairment in Parkinson's disease (PD) can be managed but effective treatments for stopping or slowing the disease process are lacking. The advent of transcriptomics studies in PD shed light on the development of promising measures to predict disease progression and discover novel therapeutic strategies.

Conclusion

We identified a two-gene signature linked to the motor progression in PD, which provides new insights into the motor prognosis of PD.

Methods

We separately analyzed the differentially expressed genes (DEGs) between PD cases and healthy controls in two cohorts using whole blood bulk transcriptome data. Based on the intersection of DEGs, we established a prognostic signature by regularized regression and Cox proportional hazards analysis. We further performed immune cell analysis and single-cell RNA sequencing analysis to study the biological features of this signature.

Objective

To reveal the potential role of transcripts in the motor impairment progression of patients with PD via transcriptome analysis.

Results

We identified a two-gene-based prognostic signature that links to PD motor progression and the two-gene signature-derived risk score was associated with several types of immune cells in blood. Notably, the fraction of neutrophils increased 5% and CD4+ T cells decreased 7% in patients with high-risk scores compared to that in patients with low-risk scores, suggesting these two types of immune cells might play key roles in the prognosis of PD. We also observed the downregulated genes in PD patients with high-risk scores that enriched in PD-associated pathways from iPSC-derived dopaminergic neurons single-cell RNA sequencing analysis.

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