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Identification of key genes and pathways in adrenocortical carcinoma: evidence from bioinformatic analysis
Mengsha Yin1, Yao Wang2, Xinhua Ren1
1Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China.
Abstract:
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis. The disease originates from the cortex of adrenal gland and lacks effective treatment. Efforts have been made to elucidate the pathogenesis of ACC, but the molecular mechanisms remain elusive. To identify key genes and pathways in ACC, the expression profiles of GSE12368, GSE90713 and GSE143383 were downloaded from the Gene Expression Omnibus (GEO) database. After screening differentially expressed genes (DEGs) in each microarray dataset on the basis of cut-off, we identified 206 DEGs, consisting of 72 up-regulated and 134 down-regulated genes in three datasets. Function enrichment analyses of DEGs were performed by DAVID online database and the results revealed that the DEGs were mainly enriched in cell cycle, cell cycle process, mitotic cell cycle, response to oxygen-containing compound, progesterone-mediated oocyte maturation, p53 signaling pathway. The STRING database was used to construct the protein-protein interaction (PPI) network, and modules analysis was performed using Cytoscape. Finally, we filtered out eight hub genes, including CDK1, CCNA2, CCNB1, TOP2A, MAD2L1, BIRC5, BUB1 and AURKA. Biological process analysis showed that these hub genes were significantly enriched in nuclear division, mitosis, M phase of mitotic cell cycle and cell cycle process. Violin plot, Kaplan-Meier curve and stage plot of these hub genes confirmed the reliability of the results. In conclusion, the results in this study provided reliable key genes and pathways for ACC, which will be useful for ACC mechanisms, diagnosis and candidate targeted treatment.
Insights
This study identifies key genes and pathways involved in adrenocortical carcinoma (ACC), a rare endocrine cancer. The findings offer potential targets for diagnosing and treating ACC, improving patient outcomes.
Area of Science:
- Endocrinology
- Oncology
- Genomics
Background:
- Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited effective treatments.
- The molecular mechanisms underlying ACC pathogenesis remain largely unknown.
- Identifying key genes and pathways is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To identify key genes and molecular pathways implicated in adrenocortical carcinoma.
- To elucidate the molecular mechanisms driving ACC development and progression.
- To provide potential targets for diagnosis and treatment of ACC.
Main Methods:
- Downloaded and analyzed gene expression profiles from GEO datasets (GSE12368, GSE90713, GSE143383).
- Identified differentially expressed genes (DEGs) and performed functional enrichment analysis using DAVID.
- Constructed a protein-protein interaction (PPI) network with Cytoscape to identify hub genes.
Main Results:
- Identified 206 DEGs (72 up-regulated, 134 down-regulated) in ACC.
- DEGs were significantly enriched in cell cycle, mitotic cell cycle, and p53 signaling pathways.
- Eight hub genes (CDK1, CCNA2, CCNB1, TOP2A, MAD2L1, BIRC5, BUB1, AURKA) were identified, enriched in nuclear division and mitosis.
Conclusions:
- This study provides a set of reliable key genes and pathways critical for ACC.
- The identified hub genes and pathways offer potential targets for ACC diagnosis and targeted therapy.
- Findings contribute to a better understanding of ACC molecular mechanisms and treatment strategies.
