Network Pharmacology Prediction: Mechanism Study of Puerarin in the Treatment of Giant Cell Tumors of Bone

Changye Zou

Status: Completed

Conditions: Giant Cell Tumors

Treatments: Genetic: gene expression levels

Study type: Observational

Funder types: Other

Identifiers

NCT06331104

ChangyeZou

Details and patient eligibility

About

Based on network pharmacology analysis, this study aims to explore the potential therapeutic targets and molecular mechanisms of puerarin on giant cell tumor of bone (GCTB) genes.

Full description

The giant cell tumor of bone's pathological genes were discovered from DisGeNET and GeneCards databases. The therapeutic genes of puerarin were gathered from Swiss Target Prediction, CTD(Comparative Toxicogenomics Database), PharmMapper, and TCMSP databases (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform). Cytoscape software was used with the MCODE algorithm to calculate key potential therapeutic targets of puerarin against GCTB. The bulk RNA-seq datasets (GSE102193) were used to identify differential expression of potential therapeutic genes. The sc RNA-seq (GSE168664) was utilized to determine the expression distribution of different cell clusters. Essential targets of puerarin against GCTB underwent function and pathway enrichment assays to elucidate biological processes and signaling pathways. Furthermore, the investigators conducted a comparison to determine if the primary biological processes and pathways following denosumab treatment exhibit resemblances to the potential mechanisms of puerarin action. Molecular docking and dynamics simulation were conducted to evaluate interactions between selected potential therapeutic targets and puerarin. Immunohistochemical (IHC) and immunofluorescence (IF) staining were performed to identify the expression of crucial markers in human GCTB tissue. Expression levels of pivotal genes in primary BMSC cells and primary GCTB cells and their alteration following puerarin treatment in primary GCTB cells were evaluated.The significance of differences between groups was estimated by the Student t-test or Wilcoxon test. In all the statistical analyses, data with two-tailed p < 0.05 were considered statistically significant.

Enrollment: 145 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosed as a patient with giant cell tumor of bone;
2. Performing surgical treatment in 1st hospital of SYSU;
3. Having complete clinical registration information;
4. Preserve surgical or puncture specimens;

Exclusion criteria

1. Non bone giant cell tumor patients;
2. No surgical treatment was performed;
3. Incomplete clinical information registration;
4. No preserved surgical or puncture specimens.

Trial design

145 participants in 2 patient groups

P27 expression groups

Description:

12 immunohistochemical sections were scored under the microscope (staining intensity scores: negative 0 points, weak 1 point, medium 2 points, strong 3 points; positive cell frequency scores: less than 5% 0 points, 2-25% 1 point, 26-50% 2 points, 51-75% 3 points, greater than 75% 4 points).

Treatment:

Genetic: gene expression levels

ESR1 expression groups

Description:

12 immunohistochemical sections were scored under the microscope (staining intensity scores: negative 0 points, weak 1 point, medium 2 points, strong 3 points; positive cell frequency scores: less than 5% 0 points, 2-25% 1 point, 26-50% 2 points, 51-75% 3 points, greater than 75% 4 points).

Treatment:

Genetic: gene expression levels