Putative Genes and Pathways Involved in the Acne Treatment of Isotretinoin via Microarray Data Analyses

Abstract

Acne is the eighth most common disease worldwide. Disease burden of acne such as anxiety, reduced self-esteem, and facial scarring lowers the life quality of acne patients. Isotretinoin is the most potent treatment for moderate-severe acne. However, the adverse events of isotretinoin especially teratogenicity limit its use. This study aims at investigating the therapeutical mechanisms of isotretinoin using bioinformatics analysis. Differentially expressed genes (DEGs) were filtered from microarray datasets GSE10432, GSE10433, and GSE11792. Functional and pathway enrichment analyses of DEGs were performed. Protein-protein interaction (PPI) network and module analyses were also conducted based on DEGs. Using isotretinoin for 1 week, LCN2, PTGES, and GDF15 were upregulated and might mediate sebocytes apoptosis and thus decreased sebum production; CCL2 originated from activated TNF signaling pathway and S100A7 could be related with "acne-flare". While treating with isotretinoin for 8 weeks, key genes were downregulated, including HMGCS1, HMGCR, FDFT1, MVD, IDI1, and FDPS, which may be associated with decreased sebum synthesis; HMGCS1, HMGCR, and FDFT1 also probably associated with apoptosis of sebocytes. There were only two common genes including ACSBG1 and BCAT2 which worked in both 1 week and 8 weeks and could associate with decreased sebum synthesis and apoptosis of sebocytes, respectively. These results indicate potential therapeutics and side effect mechanisms of isotretinoin in the acne treatment and provide a research direction to further investigate the therapeutic mechanism of isotretinoin and thus develop retinoid-like compounds with similar curative effect and without teratogenicity.

Figure 1

Volcano plots of genes expression and the common DEGs in GSE10432, GSE10433, and GSE11792. Volcano plots of genes expression in microarray data GSE10432 (a), GSE10433 (b), and GSE11792 (c). In volcano plots, green represents downregulated genes, red represents upregulated genes, and gray means no significant DEGs. UP: upregulated DEGs; DW: downregulated DEGs; NoDiff: nondifferentially expressed genes. (d) The common upregulated DEGs of GSE10432 and GSE10433. (e) The common downregulated DEGs of GSE10432 and GSE10433. (f) The common upregulated DEGs among GSE10432, GSE10433, and GSE11792. (g) The common downregulated DEGs among GSE10432, GSE10433, and GSE11792. Different colors indicate different datasets. The cross part represents the common DEGs.

Figure 2

GO and KEGG pathway enrichment analyses of the upregulated DEGs in GSE10432 and GSE10433. (a), (b), (c), and (d) represent BP, CC, MF, and KEGG, respectively. Count: number of DEGs.

Figure 3

GO and KEGG pathway enrichment analyses of the downregulated DEGs, and the PPI network in GSE10432 and GSE10433. (a), (b), and (c) represent BP, CC, and KEGG, respectively. (d) is on behalf of the PPI network of GSE10432 and GSE10433; red represents the upregulated genes, and green represents the downregulated genes. Count: number of DEGs.

Figure 4

GO and KEGG pathway enrichment analyses of the upregulated DEGs in GSE11792. (a), (b), (c), and (d) represent BP, CC, MF, and KEGG, respectively. Count: number of DEGs.

Figure 5

GO and KEGG pathway enrichment analyses of the downregulated DEGs in GSE11792. (a), (b), (c), and (d) represent BP, CC, MF, and KEGG, respectively. Count: number of DEGs.

Figure 6

The PPI network of DEGs and module analysis in GSE11792. (a) The PPI network of GSE11792 contains 303 nodes and 478 edges; five parts of the PPI network encompassed by five circles represent five modules filtered by app MCODE in Cytoscape. (b–f) represent modules 1, 2, 3, 4, and 7, respectively, which were extracted from the PPI network. Red represents the upregulated genes, and green represents the downregulated genes.