Potential therapeutic target genes for systemic lupus erythematosus: a bioinformatics analysis

Figures & data

Figure 1. Normalization of microarray dataset. (a) Before normalization of the GSE61635 dataset. (b) After normalization of the GSE61635 dataset

Figure 2. Differentially expressed genes (DEGs) between systemic lupus erythematosus (SLE) and control groups. (a) Volcano plot of GSE61635; 19 significantly expressed genes were identified. Red, green, and black dots represent upregulated, downregulated, and unchanged genes, respectively. (b) Heatmap of the top 50 DEGs from GSE61635

Table 1. Tissue-specific genes identified by BioGPS

System	Genes
Hematological	PARP9, KLF2, C15orf48, RSAD2, CYSLTR1, INHBA, AHSP, GYPB, CXCR4, LILRA5, NRBF2, GYPE, GAGE1, SPTA1, CEBPD, HSPA6, BACH2, UCHL1, TMEM140, ANXA3, CLIC2, FPR2, FFAR2, BPGM, PLOD2, HCAR3, FCRLA, EIF1AY
Immune	FBXO7, EPSTI1, SLC14A1, LILRA4, CXCR4, PALM2AKAP2, CPA3, FCRLA, CD160, KDM5D
Neurologic	ALDH5A1, RUNDC3A, SLC17A6, ERBB4, TSPAN7, PMP2, UCHL1, SOX11, NAP1L3, PEG3, TAC1, RPH3A, TSHB, GRM3, IFI27, OPCML, LIMCH1, TUBB2A, ECRG4, NRN1
Skin/Skeletal muscle	TNFAIP6, PRTG, G0S2, GATA1, EPB42, ANK1, HMBS, AHSP, GYPB, CA1, MMP8, MMP9
Respiratory	FLACC1, ADM, FAT1, P4HA2, F3, ODAM, ANXA3, JUP, IFI27, TCN1, SLPI, CAV1
Digestive	CTSE, GYPB, G0S2, SPTA1, GIPC2, GIPC2, PEG3, ANXA3, UGT2B28, DSP, CLCA1, MBL2, TSPAN8, TDO2, CA1, CLCA4, CAV1, HP, HPR, OLFM4, APOBEC3B
Circulatory	G0S2, UCHL1, CCL2, PLOD2, CAV1
Urinary/Genital	PDZK1IP1, SMIM24, TRIM6, KRT1, CXCR4, GAGE1, KCNJ16, RNASEH2A, TGM2, POTEM, DHX58, AHSP, GYPB, GMPR, FAP, ADM, TPTE, MEIS2, DSP, CCNA1, SLC26A8, TSPAN8, PAEP, CABS1, CD177
Endocrine	KCNJ16, OPRPN, ECRG4, PLOD2, TCN1, SLPI, SMR3A, CRISP3

Table 2. GO analysis of significant DEGs in SLE

Category	Term	Genes	FDR
BP	Type I interferon signaling pathway	IFITM3, RSAD2, STAT1, MX2, MX1, IFI6, ISG15, IFI35, IFIT1, IFIT3, IFIT2, OASL, IFI27, OAS1, OAS2, OAS3, IRF7, XAF1	1.20E-09
	Defense response to virus	IFITM3, RSAD2, STAT1, MX2, MX1, IFIT5, EIF2AK2, ISG15, IFIT1, DDX60, IFIT3, IFI44L, IFIT2, OASL, HERC5, CXCL10, PLSCR1, OAS1, OAS2, OAS3, DHX58, GBP1, TRIM22, APOBEC3B	6.20E-08
	Response to virus	IFITM3, RSAD2, DDX58, MX2, MX1, IFI44, EIF2AK2, IFIT1, DDX60, IFIT3, IFIT2, OASL, IFIH1, CCL8, OAS1, OAS2, OAS3, DHX58, IRF7, TRIM22	6.20E-08
	Negative regulation of viral genome replication	IFITM3, TRIM6, PLSCR1, RSAD2, OAS1, SLPI, OAS3, MX1, EIF2AK2, ISG15, IFIT1, OASL	2.69E-06
	Interferon-gamma-mediated signaling pathway	MT2A, OAS1, STAT1, OAS2, OAS3, IRF7, FCGR1A, FCGR1B, GBP1, TRIM22, OASL	0.007775401
	Innate immune response	CRISP3, IFIT5, LY96, DDX60, LILRA5, IFIH1, HERC5, DHX58, TAC1, MBL2, ZBP1, NLRP2B, DDX58, MX2, MX1, DEFB114, EIF2AK2, DEFB108B, MID2, CLEC4D, AIM2, VNN1, SLPI, IRF7, SERPING1, TLR5, FRK, APOBEC3B	0.013089362
CC	Hemoglobin complex	HBZ, HBM, AHSP, HBD, HBQ1	0.023035163
	Cortical cytoskeleton	TMOD1, DMTN, GYPC, EPB42, EPB41, SLC4A1	0.023035163
	Extracellular space	LGALS3BP, IL1RN, C2ORF40, TNFAIP6, CRISP3, LECT2, HP, ADM, PTPRG, TNFSF13B, SMR3B, ADAMTS3, ZNF649, TNFSF10, FAM3B, TSHB, MBL2, CPA3, KRT1, NOG, WNT5A, OLFM4, MMP8, MMP9, F3, OPRPN, SFRP2, OLFM3, SLPI, OAS3, SERPING1, HIST1H2BD, HIST1H2BC, SERPINB10, NLGN1, NRN1, SEMA3D, LRRC17, LY96, STC1, C9ORF72, FBLN5, PRTG, SELENBP1, APELA, CCL8, SPOCK3, CLCA1, CCL2, SLIT2, TAC1, LRRC4C, SNCA, ODAM, BMP5, CXCL10, CXCL11, LRG1, COL1A2, FAP, TCN1, LEP	0.004656585
MF	Metalloendopeptidase activity	ADAMDEC1, ADAM32, MMP8, MMP9, ADAM18, ADAMTS3, KEL, MMP16, FAP, MMP26, CLCA1, TLL1, CLCA4	0.021510128
	2ʹ-5ʹ-oligoadenylate synthetase activity	OAS1, OAS2, OAS3, OASL	0.021510128
	Double-stranded RNA binding	IFIH1, OAS1, DDX58, OAS2, OAS3, DHX58, EIF2AK2, DDX60, OASL	0.037427071

Table 3. KEGG pathway analysis of significant DEGs in SLE

Pathway ID	Name	Genes	P-Value
hsa05164	Influenza A	RSAD2, DDX58, STAT1, HSPA6, MX1, EIF2AK2, NXT2, IFIH1, CXCL10, OAS1, OAS2, OAS3, TNFSF10, IRF7, CCL2	3.55E-04
hsa05162	Measles	IFIH1, OAS1, DDX58, STAT1, OAS2, OAS3, MX1, HSPA6, IRF7, TNFSF10, EIF2AK2	0.004053153
hsa00860	Porphyrin and chlorophyll metabolism	ALAS2, HEPH, FECH, HMBS, BLVRB, UGT2B28	0.006044328
hsa05168	Herpes simplex infection	IFIH1, OAS1, DDX58, STAT1, OAS2, OAS3, IRF7, EIF2AK2, CCL2, FOS, IFIT1	0.033041831
hsa05160	Hepatitis C	OAS1, DDX58, STAT1, OAS2, CLDN8, OAS3, IRF7, EIF2AK2, IFIT1	0.033050818
hsa04622	RIG-I-like receptor signaling pathway	IFIH1, CXCL10, DDX58, DHX58, IRF7, ISG15	0.046053009
hsa05144	Malaria	GYPA, GYPC, GYPB, CCL2, ACKR1	0.047754191

Figure 3. Distribution of differentially expressed genes (DEGs) in systemic lupus erythematosus (SLE) for GO enrichment

Figure 4. KEGG enrichment analysis of differentially expressed genes (DEGs). Strength of the color represents the p-value (from the lowest in green to the highest in red), and the bubble size represents the number of DEGs

Figure 5. The PPI network of differentially expressed genes (DEGs). (a) Top 20 DEGs visualized based on the Closeness algorithm analysis in Cytoscape. (b) Top 20 DEGs based on Closeness score ranking

Figure 6. Key genes between hub genes and tissue-specific genes

Figure 7. Concentration of CCL2, MMP9, GATA1, and RSAD2 in the serum. (a–d) Concentration of CCL2, MMP9, GATA1, and RSAD2 in the serum. Data are presented as mean ± SD (n ≥ 15). * p < 0.05, **p < 0.01, *** p< 0.005 vs Control; NS, no statistical significance vs Control