Identification of the disulfidptosis-related gene IQGAP1 as a potential diagnostic biomarker in Parkinson's disease.

BACKGROUND: Parkinson's disease is the second most common and fastest-growing neurodegenerative disorder worldwide. However, its complex pathogenic mechanisms remain incompletely understood, and effective therapeutic strategies are still lacking. Disulfidptosis is a newly identified form of regulated cell death that has been shown to be closely associated with multiple diseases; nevertheless, its role in Parkinson's disease has not yet been elucidated. In this study, we systematically investigated the expression patterns and potential functions of disulfidptosis-related differentially expressed genes that are significantly associated with Parkinson's disease risk, using bulk transcriptomic data and single-cell RNA sequencing analyses.

METHODS: We integrated single-cell RNA sequencing data with large-scale transcriptomic datasets to construct a disulfidptosis-related diagnostic model for Parkinson's disease. First, twenty-five known disulfidptosis-related genes were collected from published literature and public databases. Differential expression analysis of GEO datasets was then performed to identify significantly differentially expressed genes between Parkinson's disease and healthy control samples, which were subsequently used to build an initial diagnostic model. The expression profiles of key genes were further validated in external cohorts to enhance the robustness and reliability of the model. Next, single-cell RNA sequencing data from patients with Parkinson's disease were incorporated to refine the identification of DRGs that were significantly associated with disease risk. Finally, quantitative real-time reverse transcription PCR was employed to experimentally validate the expression of the critical genes.

RESULTS: We identified four DRGs in total. Using least absolute shrinkage and selection operator regression and random forest algorithms, three hub genes with diagnostic potential were further screened. After validation in external datasets and at the single-cell level, IQGAP1 was ultimately confirmed as the key gene by quantitative real-time reverse transcription PCR, showing significantly upregulated expression in Parkinson's disease samples.

CONCLUSION: This study provides the first evidence suggesting that disulfidptosis-related genes may be involved in the pathogenesis of Parkinson's disease and highlights IQGAP1 as a key molecule with potential value in Parkinson's disease risk assessment and diagnosis. These findings not only offer a new perspective for elucidating the molecular mechanisms underlying Parkinson's disease, but also provide a theoretical basis for identifying potential biomarkers and optimizing individualized therapeutic strategies, thereby further promoting the application of precision medicine in the field of Parkinson's disease.