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

Treatment of Giant Cell Bone Tumor With Purerin: New Insights From Network Pharmacology, Bioinformatics Analysis, and Experimental Verification

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.

Study Overview

• Status: Completed
• Conditions: Giant Cell Tumors
• Intervention / Treatment: Genetic: gene expression levels

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 145

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 518010
      • Churong Yan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

1st hospital of SYSU provides diagnosis and treatment that meets the inclusion criteria.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
P27 expression groups; 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).	Genetic: gene expression levels; 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).
ESR1 expression groups; 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).	Genetic: gene expression levels; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
P27 expression levels	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).	2023-05-18 - 2023-08-31
ESR1 expression levels	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).	2023-05-18 - 2023-08-31

Collaborators and Investigators

• Sponsor: Changye Zou
• Investigators: Principal Investigator: Changye Zou, MD, First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2012
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 30, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Treatment; Traditional Chinese medicine; Puerarin; Giant Cell Tumors; Network Pharmacology
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Giant Cell Tumors
• Other Study ID Numbers: ChangyeZou

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The datasets are available from the corresponding author (zouchy@mail.sysu.edu.cn) on reasonable request after SCI online.
• IPD Sharing Time Frame: SCI online. The datasets are available from the corresponding author on reasonable request.
• IPD Sharing Access Criteria: The datasets are available from the corresponding author (zouchy@mail.sysu.edu.cn) on reasonable request after SCI online.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No