Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Basic Helix-Loop-Helix Transcription Factors / genetics
-
Basic-Leucine Zipper Transcription Factors / genetics
-
Biomarkers / analysis*
-
Biomarkers / metabolism
-
Computational Biology / methods*
-
DNA-Binding Proteins / genetics
-
E2F1 Transcription Factor / genetics
-
Early Growth Response Protein 3 / genetics
-
Gene Expression Profiling / methods*
-
Homeodomain Proteins / genetics
-
Humans
-
Parkinson Disease / genetics*
-
Parkinson Disease / metabolism*
-
Proto-Oncogene Proteins / genetics
-
Regulatory Factor X Transcription Factors
-
Regulatory Factor X1
-
STAT4 Transcription Factor / genetics
-
T-Cell Acute Lymphocytic Leukemia Protein 1
-
Transcription Factors / genetics
Substances
-
Basic Helix-Loop-Helix Transcription Factors
-
Basic-Leucine Zipper Transcription Factors
-
Biomarkers
-
DNA-Binding Proteins
-
E2F1 Transcription Factor
-
E2F1 protein, human
-
EGR3 protein, human
-
HLF protein, human
-
Homeodomain Proteins
-
NKX3-1 protein, human
-
Proto-Oncogene Proteins
-
RFX1 protein, human
-
Regulatory Factor X Transcription Factors
-
Regulatory Factor X1
-
STAT4 Transcription Factor
-
STAT4 protein, human
-
T-Cell Acute Lymphocytic Leukemia Protein 1
-
Transcription Factors
-
TAL1 protein, human
-
Early Growth Response Protein 3
Grants and funding
This research is supported by Liaoning Science and Technology Plan Projects (No. 2008820). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.