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Isolation and Characterization of Patient-derived Pancreatic Ductal Adenocarcinoma Organoid Models
Published on: January 14, 2020
A network pharmacology-based investigation of emodin against pancreatic adenocarcinoma
Xueying Shi1,2, Bingqian Huang1,2, Jingyi Zhu1,2
1Clinical Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Abstract:
Pancreatic adenocarcinoma (PAAD) is one of the most common malignancies worldwide with an increasing incidence and poor outcome due to the lack of effective diagnostic and treatment methods. Emerging evidence implicates that emodin displays extensive spectrum anticancer properties. Differential expression genes in PAAD patients were analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) website, and the targets of emodin were obtained via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Subsequently, enrichment analyses were performed using R software. A protein-protein interaction (PPI) network was constructed by STRING database and Cytoscape software was used to identify the hub genes. Prognostic value and immune infiltration landscapes were explored through Kaplan-Meier plotter (KM plotter) website and the Single-Sample Gene Set Enrichment Analysis package of R. Finally, molecular docking was used to computationally verify the interaction of ligand and receptor proteins. A total of 9191 genes were significantly differentially expressed in PAAD patients and 34 potential targets of emodin were obtained. Intersections of the 2 groups were considered as potential targets of emodin against PAAD. Functional enrichment analyses illustrated that these potential targets were linked to numerous pathological processes. Hub genes identified through PPI networks were correlated with poor prognosis and infiltration level of different immune cells in PAAD patients. Perhaps emodin interacted with the key molecules and regulate the activity of them. We revealed the inherent mechanism of emodin against PAAD with the aid of network pharmacology, which provided reliable evidence and a novel guideline for clinical treatment.
Insights
Emodin shows potential anticancer effects against pancreatic adenocarcinoma (PAAD) by targeting key genes. Network pharmacology reveals its mechanism, offering new therapeutic guidelines for PAAD treatment.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Pancreatic adenocarcinoma (PAAD) presents a global health challenge with increasing incidence and poor patient outcomes.
- Current diagnostic and treatment strategies for PAAD remain limited.
- Emodin, a natural compound, exhibits promising broad-spectrum anticancer properties.
Purpose of the Study:
- To investigate the underlying molecular mechanisms of emodin as an anticancer agent against PAAD using network pharmacology.
- To identify potential therapeutic targets of emodin in PAAD.
- To explore the prognostic value and immune infiltration landscape associated with emodin's targets in PAAD.
Main Methods:
- Differential gene expression analysis using GEPIA.
- Target identification via Traditional Chinese Medicine Systems Pharmacology Database.
- Enrichment analysis, protein-protein interaction network construction (STRING, Cytoscape).
- Prognostic and immune infiltration analysis (KM plotter, R package).
- Molecular docking for interaction verification.
Main Results:
- Identified 9191 differentially expressed genes in PAAD and 34 potential emodin targets.
- Functional enrichment revealed targets involved in critical pathological processes.
- Key hub genes were associated with poor prognosis and altered immune cell infiltration in PAAD.
- Molecular docking supported the interaction between emodin and target proteins.
Conclusions:
- Network pharmacology elucidates emodin's mechanism against PAAD by modulating key molecules.
- Identified hub genes offer prognostic and potential therapeutic insights.
- Emodin presents a promising novel therapeutic strategy for pancreatic adenocarcinoma.
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