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Identification of hub genes and pathways in adrenocortical carcinoma by integrated bioinformatic analysis
Jinshuai Guo1, Yinzhong Gu2, Xiaoyu Ma1
1Department of Predictive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng, China.
Abstract:
Adrenocortical carcinoma (ACC), a rare malignant neoplasm originating from adrenal cortical cells, has high malignancy and few treatments. Therefore, it is necessary to explore the molecular mechanism of tumorigenesis, screen and verify potential biomarkers, which will provide new clues for the treatment and diagnosis of ACC. In this paper, three gene expression profiles (GSE10927, GSE12368 and GSE90713) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained using the Limma package. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched by DAVID. Protein-protein interaction (PPI) network was evaluated by STRING database, and PPI network was constructed by Cytoscape. Finally, GEPIA was used to validate hub genes' expression. Compared with normal adrenal tissues, 74 up-regulated DEGs and 126 down-regulated DEGs were found in ACC samples; GO analysis showed that up-regulated DEGs were enriched in organelle fission, nuclear division, spindle, et al, while down-regulated DEGs were enriched in angiogenesis, proteinaceous extracellular matrix and growth factor activity; KEGG pathway analysis showed that up-regulated DEGs were significantly enriched in cell cycle, cellular senescence and progesterone-mediated oocyte maturation; Nine hub genes (CCNB1, CDK1, TOP2A, CCNA2, CDKN3, MAD2L1, RACGAP1, BUB1 and CCNB2) were identified by PPI network; ACC patients with high expression of 9 hub genes were all associated with worse overall survival (OS). These hub genes and pathways might be involved in the tumorigenesis, which will offer the opportunities to develop the new therapeutic targets of ACC.
Insights
Adrenocortical carcinoma (ACC) research identified key genes involved in cell division and growth. High expression of these genes correlates with poorer patient survival, offering potential new therapeutic targets for this rare cancer.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with limited treatment options.
- Understanding ACC tumorigenesis is crucial for developing novel diagnostic and therapeutic strategies.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) and hub genes in ACC.
- To explore molecular mechanisms and potential biomarkers for ACC treatment and diagnosis.
Main Methods:
- Downloaded and analyzed three gene expression profiles (GSE10927, GSE12368, GSE90713) from the GEO database.
- Utilized Limma for DEG analysis, DAVID for GO and KEGG enrichment, STRING and Cytoscape for PPI network construction, and GEPIA for hub gene validation.
Main Results:
- Identified 74 up-regulated and 126 down-regulated DEGs in ACC.
- Up-regulated DEGs are enriched in cell cycle and nuclear division pathways; down-regulated DEGs are linked to angiogenesis.
- Nine hub genes (CCNB1, CDK1, TOP2A, CCNA2, CDKN3, MAD2L1, RACGAP1, BUB1, CCNB2) were identified, with high expression correlating to worse overall survival.
Conclusions:
- The identified hub genes and enriched pathways are potentially involved in ACC tumorigenesis.
- These findings offer new therapeutic targets and diagnostic opportunities for adrenocortical carcinoma.
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