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Identification of important invasion and proliferation related genes in adrenocortical carcinoma
Ali Mohamed Alshabi1, Basavaraj Vastrad2, Ibrahim Ahmed Shaikh3
1Department of Clinical Pharmacy, College of Pharmacy, Najran University, Najran, Saudi Arabia.
Abstract:
Adrenocortical carcinoma (ACC) is an end-stage hormonal syndrome. Although profound attempts have been made to illuminate the pathogenesis, the molecular mechanisms of ACC remain to be clarified. To identify the important genes in the progression of ACC, microarray datasets GSE19775 was downloaded from the gene expression omnibus database. The differentially-expressed genes (DEGs) were identified, and pathway and GO enrichment analyses were performed. The protein-protein interaction (PPI) network was constructed and the module analysis was performed using the protein interaction network analysis and Cytoscape. Also constructed target genes-miRNA regulatory network and target genes-TF regulatory network. Correlation of the hub genes were analyzed in The Cancer Genome Atlas. The prognostic values of hub genes were further validated by online tool UALCAN. Mutation analysis was done by online tool CBio Cancer Genomics Portal. A total of 884 DEGs were identified, with 441 in up regulation and 443 in down regulation. Pathways in catecholamine biosynthesis, aldosterone synthesis and secretion, pyrimidine deoxyribonucleosides salvage and systemic lupus erythematosus were the most significantly enriched for DEGs (up and down regulated). Blood vessel morphogenesis and cell cycle phase transition were the most significantly enriched term in biological processes, while extracellular matrix and chromosome, centromeric region were in cellular component and heparin binding and protein dimerization activity were in molecular function. Among the PPI networks and its module, target genes-miRNA regulatory network and target genes-TF regulatory network, hub genes were YWHAZ, FN1, GRK5, VCAM1, GATA6, TXNIP, HSPA1A, and F11R. Hub genes such as YWHAZ, STAT1, ICAM1, SH3BP5, CD83, FN1, TK1, HIST1H1C, CABLES1, and MCM3 were associated with poor overall survival, while hub genes such as STAT1, ICAM1, CD83, FN1, TK1, HIST1H1C, and MCM3 were highly expressed in stage 4. In conclusion, DEGs and hub genes diagnosed in this study may deepen our understanding of molecular mechanisms underlying the progression of ACC, and provide important targets for diagnosis and treatment of ACC.
Insights
This study identifies key genes involved in adrenocortical carcinoma (ACC) progression. These differentially-expressed genes (DEGs) and hub genes offer potential new targets for ACC diagnosis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poorly understood molecular mechanisms.
- Identifying key genes is crucial for understanding ACC pathogenesis and developing targeted therapies.
Purpose of the Study:
- To identify differentially-expressed genes (DEGs) and hub genes in adrenocortical carcinoma (ACC) progression.
- To explore the molecular mechanisms and potential therapeutic targets for ACC.
Main Methods:
- Microarray data (GSE19775) analysis to identify DEGs.
- Pathway and Gene Ontology (GO) enrichment analyses.
- Construction of protein-protein interaction (PPI), miRNA-target, and TF-target regulatory networks.
- Validation of hub gene correlations, prognostic values, and mutations using TCGA, UALCAN, and CBioPortal.
Main Results:
- Identified 884 DEGs (441 upregulated, 443 downregulated).
- Enriched pathways included catecholamine biosynthesis and aldosterone synthesis; key biological processes involved blood vessel morphogenesis and cell cycle.
- Hub genes like YWHAZ, FN1, and GRK5 were identified, with several associated with poor prognosis and advanced stage ACC.
Conclusions:
- The identified DEGs and hub genes provide insights into the molecular underpinnings of ACC progression.
- These genes represent potential biomarkers for ACC diagnosis and therapeutic targets.
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