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Published on: July 22, 2020
Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma
Fangshi Xu1,2, Peng Zhang1, Miao Yuan2
1Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710000, P.R. China.
Abstract:
The molecular mechanisms of adrenocortical carcinoma (ACC) carcinogenesis and progression remain unclear. In the present study, three microarray datasets from the Gene Expression Omnibus database were screened, which identified a total of 96 differentially expressed genes (DEGs). A protein-protein interaction network (PPI) was established for these DEGs and module analysis was performed using STRING and Cytoscape. A total of eight hub genes were identified from the most significant module; namely, calponin 1 (CNN1), myosin light chain kinase (MYLK), cysteine and glycine rich protein 1 (CSRP1), myosin heavy chain 11 (MYH11), fibulin extracellular matrix protein 2 (EFEMP2), fibulin 1 (FBLN1), microfibril associated protein 4 (MFAP4) and fibulin 5 (FBLN5). The biological functions of these hub genes were analyzed using the DAVID online tool. Changes in the expression of hub genes did not affect overall survival; however, downregulated EFEMP2 decreased disease-free survival. CSRP1 and MFAP4 expression levels were associated with adverse clinicopathological features. In conclusion, although all eight hub genes were downregulated in ACC, they appeared to have important functions in ACC carcinogenesis and progression. Identification of these genes complements the genetic expression profile of ACC and provides insight for the diagnosis, treatment and prognosis of ACC.
Insights
This study identified eight key genes involved in adrenocortical carcinoma (ACC) development. While generally downregulated, these genes, including EFEMP2, CSRP1, and MFAP4, offer potential diagnostic and prognostic insights for ACC.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poorly understood molecular drivers.
- Identifying key genes in ACC carcinogenesis and progression is crucial for improving patient outcomes.
Purpose of the Study:
- To identify and analyze differentially expressed genes (DEGs) and hub genes in adrenocortical carcinoma (ACC).
- To investigate the functional roles and prognostic significance of identified hub genes in ACC.
Main Methods:
- Utilized three Gene Expression Omnibus microarray datasets to identify 96 DEGs in ACC.
- Constructed a protein-protein interaction (PPI) network using STRING and Cytoscape to identify eight hub genes.
- Performed functional enrichment analysis using the DAVID online tool.
Main Results:
- Eight hub genes were identified: CNN1, MYLK, CSRP1, MYH11, EFEMP2, FBLN1, MFAP4, and FBLN5.
- All identified hub genes were downregulated in ACC.
- Downregulated EFEMP2 correlated with decreased disease-free survival; CSRP1 and MFAP4 linked to adverse clinicopathological features.
Conclusions:
- The identified hub genes play significant roles in ACC carcinogenesis and progression despite their downregulation.
- These findings enhance the understanding of ACC's genetic landscape.
- The study provides potential targets for ACC diagnosis, treatment, and prognosis.

