Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
PLoS One. 2012;7(12):e52319. doi: 10.1371/journal.pone.0052319. Epub 2012 Dec 28.
Parkinson disease (PD) progresses relentlessly and affects approximately 4% of the population aged over 80 years old. It is difficult to diagnose in its early stages. The purpose of our study is to identify molecular biomarkers for PD initiation using a computational bioinformatics analysis of gene expression. We downloaded the gene expression profile of PD from Gene Expression Omnibus and identified differentially coexpressed genes (DCGs) and dysfunctional pathways in PD patients compared to controls. Besides, we built a regulatory network by mapping the DCGs to known regulatory data between transcription factors (TFs) and target genes and calculated the regulatory impact factor of each transcription factor. As the results, a total of 1004 genes associated with PD initiation were identified. Pathway enrichment of these genes suggests that biological processes of protein turnover were impaired in PD. In the regulatory network, HLF, E2F1 and STAT4 were found have altered expression levels in PD patients. The expression levels of other transcription factors, NKX3-1, TAL1, RFX1 and EGR3, were not found altered. However, they regulated differentially expressed genes. In conclusion, we suggest that HLF, E2F1 and STAT4 may be used as molecular biomarkers for PD; however, more work is needed to validate our result.
帕金森病（PD）不断进展，影响着大约 4%的 80 岁以上人群。它在早期难以诊断。我们的研究目的是使用基因表达的计算生物信息学分析，来确定 PD 发病的分子生物标志物。我们从基因表达综合数据库下载了 PD 的基因表达谱，并鉴定了 PD 患者与对照组相比差异共表达基因（DCGs）和功能失调通路。此外，我们通过将 DCGs 映射到转录因子（TFs）和靶基因之间的已知调控数据，构建了一个调控网络，并计算了每个转录因子的调控影响因子。结果，共鉴定出与 PD 发病相关的 1004 个基因。这些基因的通路富集表明，PD 中蛋白质周转的生物学过程受损。在调控网络中，HLF、E2F1 和 STAT4 的表达水平在 PD 患者中发生改变。NKX3-1、TAL1、RFX1 和 EGR3 等其他转录因子的表达水平未发现改变，但它们调节差异表达基因。总之，我们认为 HLF、E2F1 和 STAT4 可以作为 PD 的分子生物标志物；但是，需要进一步的工作来验证我们的结果。
