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Updated: Nov 13, 2025
Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
Published on: October 3, 2025
Identification of potential and novel target genes in pituitary prolactinoma by bioinformatics analysis
Vikrant Ghatnatti1, Basavaraj Vastrad2, Swetha Patil3
1Department of Endocrinology, J N Medical College, Belagavi and KLE Academy of Higher Education & Research 590010, Karnataka, India.
Abstract:
Pituitary prolactinoma is one of the most complicated and fatally pathogenic pituitary adenomas. Therefore, there is an urgent need to improve our understanding of the underlying molecular mechanism that drives the initiation, progression, and metastasis of pituitary prolactinoma. The aim of the present study was to identify the key genes and signaling pathways associated with pituitary prolactinoma using bioinformatics analysis. Transcriptome microarray dataset GSE119063 was downloaded from Gene Expression Omnibus (GEO) database. Limma package in R software was used to screen DEGs. Pathway and Gene ontology (GO) enrichment analysis were conducted to identify the biological role of DEGs. A protein-protein interaction (PPI) network was constructed and analyzed by using HIPPIE database and Cytoscape software. Module analyses was performed. In addition, a target gene-miRNA regulatory network and target gene-TF regulatory network were constructed by using NetworkAnalyst and Cytoscape software. Finally, validation of hub genes by receiver operating characteristic (ROC) curve analysis. A total of 989 DEGs were identified, including 461 up regulated genes and 528 down regulated genes. Pathway enrichment analysis showed that the DEGs were significantly enriched in the retinoate biosynthesis II, signaling pathways regulating pluripotency of stem cells, ALK2 signaling events, vitamin D3 biosynthesis, cell cycle and aurora B signaling. Gene Ontology (GO) enrichment analysis showed that the DEGs were significantly enriched in the sensory organ morphogenesis, extracellular matrix, hormone activity, nuclear division, condensed chromosome and microtubule binding. In the PPI network and modules, SOX2, PRSS45, CLTC, PLK1, B4GALT6, RUNX1 and GTSE1 were considered as hub genes. In the target gene-miRNA regulatory network and target gene-TF regulatory network, LINC00598, SOX4, IRX1 and UNC13A were considered as hub genes. Using integrated bioinformatics analysis, we identified candidate genes in pituitary prolactinoma, which might improve our understanding of the molecular mechanisms of pituitary prolactinoma.
Insights
This study identifies key genes and pathways involved in pituitary prolactinoma development using bioinformatics. Findings highlight potential molecular targets for understanding and treating this complex pituitary adenoma.
Area of Science:
- Endocrinology
- Molecular Biology
- Bioinformatics
Background:
- Pituitary prolactinoma is a complex and often fatal pituitary adenoma.
- Understanding the molecular mechanisms driving prolactinoma initiation, progression, and metastasis is crucial.
Purpose of the Study:
- To identify key genes and signaling pathways associated with pituitary prolactinoma using bioinformatics analysis.
- To uncover potential molecular targets for improved understanding and treatment of pituitary prolactinoma.
Main Methods:
- Downloaded and analyzed transcriptome microarray dataset GSE119063 from the Gene Expression Omnibus (GEO) database.
- Utilized Limma package in R for differential gene expression (DEG) screening.
- Performed pathway and Gene Ontology (GO) enrichment analyses.
- Constructed and analyzed protein-protein interaction (PPI) networks, and gene-miRNA/TF regulatory networks using HIPPIE, NetworkAnalyst, and Cytoscape.
- Validated hub genes using receiver operating characteristic (ROC) curve analysis.
Main Results:
- Identified 989 differentially expressed genes (DEGs), including 461 upregulated and 528 downregulated.
- Pathway analysis revealed significant enrichment in retinoate biosynthesis II, stem cell pluripotency signaling, ALK2 signaling, vitamin D3 biosynthesis, cell cycle, and aurora B signaling.
- GO analysis indicated enrichment in sensory organ morphogenesis, extracellular matrix, hormone activity, nuclear division, condensed chromosome, and microtubule binding.
- Identified hub genes including SOX2, PRSS45, CLTC, PLK1, B4GALT6, RUNX1, GTSE1, LINC00598, SOX4, IRX1, and UNC13A.
Conclusions:
- Integrated bioinformatics analysis successfully identified candidate genes and pathways implicated in pituitary prolactinoma.
- These findings offer novel insights into the molecular mechanisms underlying pituitary prolactinoma.
- The identified hub genes represent potential therapeutic targets for pituitary prolactinoma.
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