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Updated: Feb 10, 2026

Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
Published on: October 3, 2025
Gene expression profiles and pathway enrichment analysis of human osteosarcoma cells exposed to sorafenib
Zhehao Dai1, Haoyu Tang2, Yue Pan1
1Department of Spine Surgery The Second Xiangya Hospital Central South University Changsha China.
Abstract:
Sorafenib is an inhibitor of a variety of tyrosine kinase receptors used to treat various cancers including hepatocellular, renal cell and thyroid carcinoma. It has been shown to change various targets associated with osteosarcoma, but the detailed mechanism remains unclear. In order to identify key genes, enriched pathways and important modules during the exposure of human osteosarcoma cells to sorafenib, data for gene expression profiles (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53155) were downloaded from the GEO database. In total, 61 differentially expressed genes (DEGs) were identified by the R bioconductor packages. Functional and enrichment analyses of DEGs were performed using the DAVID database. These revealed that DEGs were enriched in biological processes, molecular function and KEGG pathway of inflammatory immune response and angiogenesis. A protein-protein interaction network was constructed by string and visualized in cytoscape, and eight genes were selected as hubs: IL8,CXCL2,PTGS2,FOS,CXCL1, C3,EHMT2 and PGF. Subsequently, only one cluster was identified by mcode, which consisted of six nodes (CXCL1,CXCL2,PTGS2,FOS, C3 and PGF) and nine edges. PGF was the seed gene in this cluster. In conclusion, the results of this data mining and integration should help in revealing new mechanisms and targets of sorafenib in inhibiting osteosarcoma.
Insights
Sorafenib, a tyrosine kinase inhibitor, impacts osteosarcoma by altering inflammatory and angiogenesis pathways. Key genes like PGF were identified, offering new therapeutic targets for this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Sorafenib is a multi-kinase inhibitor used in treating various cancers.
- Its precise mechanism in osteosarcoma remains incompletely understood.
- Identifying key molecular targets is crucial for optimizing osteosarcoma treatment.
Purpose of the Study:
- To identify key genes, enriched pathways, and critical modules in human osteosarcoma cells treated with sorafenib.
- To elucidate the molecular mechanisms underlying sorafenib's effects on osteosarcoma.
- To uncover potential novel therapeutic targets for osteosarcoma.
Main Methods:
- Gene expression profiles of osteosarcoma cells exposed to sorafenib were analyzed using data from the GEO database (GSE53155).
- Differentially expressed genes (DEGs) were identified using R bioconductor packages.
- Functional enrichment analyses (DAVID database) and protein-protein interaction network construction (STRING, Cytoscape) were performed.
Main Results:
- Sixty-one differentially expressed genes (DEGs) were identified.
- Enrichment analysis revealed significant involvement of inflammatory immune response and angiogenesis pathways.
- Eight hub genes were identified, including IL8, CXCL2, PTGS2, FOS, CXCL1, C3, EHMT2, and PGF. A key module highlighted PGF as the seed gene.
Conclusions:
- This study reveals that sorafenib influences osteosarcoma through modulation of inflammatory and angiogenesis pathways.
- Key genes such as PGF, CXCL1, and CXCL2 are central to sorafenib's mechanism in osteosarcoma.
- The findings provide a foundation for understanding novel therapeutic strategies and targets for osteosarcoma treatment.
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