Integrative analyses of hub genes and their association with immune infiltration in adipose tissue, liver tissue and skeletal muscle of obese patients after bariatric surgery

Figures & data

Table 1. Detailed information on the included GEO datasets

Series	Platform	Analysis type	Tissue	Number of tissue samples from obese subjects		Title of study	Year	Reference
				Before BS	After BS
GSE59034	GPL11532	Array	Adipose tissue	n = 16	n = 16	A Memory for Obesity in Adipose Tissue	2017	PMID: 30332637
GSE66921	GPL13607	Array	Adipose tissue	n = 4	n = 4	Transcriptional profiling of subcutaneous adipose tissue of morbidly obese subjects before and after 2 years of bariatric surgery	2017	NA
GSE106737	GPL16686	Array	Liver	n = 41	n = 41	Microarray analysis of liver biopsies at baseline and after one year follow up from 21 patients with histologically proven NASH (responders, bariatric surgery)	2019	PMID: 31701087
GSE134913	GPL26966	Array	Skeletal muscle	n = 14	n = 28	Dynamic changes of muscle insulin sensitivity after metabolic surgery I	2019	PMID: 31519890
GSE5109	GPL570	Array	Skeletal muscle	n = 3	n = 3	Gastric Bypass Human Obese Muscle	2006	PMID: 16849634

Figure 1. Flow chart of the study design.

Figure 2. Visualization of DEGs in adipose tissue, liver tissue and skeletal muscle before and after BS. (a, c, e) Heatmap showing the expression of representative DEGs of each sample in adipose tissue (combination and normalization of GSE59034 and GSE66921), liver tissue (GSE106737) and skeletal muscle (combination and normalization of GSE134913 and GSE5109). The top 10 upregulated DEGs and top 10 downregulated DEGs ranked by logFC are shown as representative DEGs. In adipose tissue, only 4 upregulated DEGs were observed. (b, d, f,) DEGs in adipose tissue, liver tissue and skeletal muscle are presented in a volcano map. The representative DEGs were labelled with the gene names.

Figure 3. Venn diagram and enrichment analysis of DEGs from adipose tissue, liver tissue and skeletal muscle before and after BS.

(a) Venn diagram of DEGs in adipose tissue, liver tissue and skeletal muscle. The common DEGs were defined as the intersection of DEGs in at least two metabolic tissues. A total of 121 common DEGs were identified. (b) KEGG analysis of common DEGs. (c) GO analysis of common DEGs. The cut-off criteria for both the KEGG and GO analysis was q-value<0.05.

Figure 4. GSVA displaying pathway differences in adipose tissue, liver tissue and skeletal muscle before and after BS. GSVA was performed using the ‘GSVA’ R package to identify the pathway alterations in adipose tissue, liver tissue and skeletal muscle after BS. (a) Heatmap of GSVA in adipose tissue. (b) Heatmap of GSVA in liver tissue. (c) Heatmap of GSVA in skeletal muscle. Pathways with p< 0.05 were considered statistically significant.

Figure 5. Identification of hub genes and prediction of TF, miRNA and drug-gene networks.(a) Construction of the PPI network of the 121 common DEGs. (b) Identification of hub genes by PPI network. (c) Construction of the hub gene-TF network. (d) Construction of hub genes-miRNA network. (e) Hub gene-drug interaction network.

Figure 6. Analysis of immune cell infiltration in adipose tissue, liver tissue and skeletal muscle before and after BS according to the CIBERSORT algorithm. The differences in the relative percentages of infiltrating immune cells after BS were calculated by the CIBERSORT algorithm. The relative abundance of 22 different immune cells in (a) adipose tissue, (b) liver tissue and (c) skeletal muscle before and after BS. The Wilcoxon test was applied, and p< 0.05 was considered statistically significant.

Figure 7. Association of hub genes and infiltrating immune cells in adipose tissue, liver tissue and skeletal muscle. Correlations of hub gene expression and infiltrating immune cells were analysed by Spearman correlation analysis. The heatmaps present correlations of hub gene expression and infiltrating immune cells in (a) adipose tissue, (b) liver tissue and (c) skeletal muscle. *p < 0.05.

Figure 8. Validation of hub genes in adipose tissue. (a) Expression of hub genes in adipose tissue of obese subjects before (n = 42) and after BS (n = 42) was validated in the GSE72158 dataset. (b) Expression changes of hub genes in adipose tissue between obese (n = 10) and normal weight (n = 10) people were validated in the GSE151839 dataset. (c) Expression changes of hub genes in adipose tissue between obese (n = 5) and lean (n = 5) B6 mice were validated in the Attie Lab Diabetes database. The Wilcoxon test was performed. *p < 0.05.

Data availability statement

The data that support the findings of this study are available in the GEO database (http://www.ncbi.nlm.nih.gov/geo) under reference numbers [GSE59034, GSE66921, GSE106737, GSE134913, GSE5109, GSE72158, and GSE151839].