Bioinformation Analysis Reveals IFIT1 as Potential Biomarkers in Central Nervous System Tuberculosis

Figures & data

Table 1 Differentially Expressed Genes

Gene Symbol	Adjusted P-value	Fold Change	Gene Title
Up-regulated genes
BATF2	1.44E-24	3.21	Basic leucine zipper ATF-like transcription factor 2
ANKRD22	2.30E-22	2.80	Ankyrin repeat domain 22
FCGR1CP	9.90E-23	2.75	Fc fragment of IgG receptor Ic, pseudogene
FCGR1A	1.90E-20	2.67	Fc fragment of IgG receptor Ia
FCGR1B	8.55E-22	2.65	Fc fragment of IgG receptor Ib
C1QB	1.97E-20	2.64	Complement C1q B chain
RSAD2	1.47E-16	2.41	Radical S-adenosyl methionine domain containing 2
GBP5	1.20E-26	2.17	Guanylate binding protein 5
EPSTI1	2.17E-24	2.13	Epithelial stromal interaction 1
CARD17	1.84E-18	2.09	Caspase recruitment domain family member 17
IFIT3	7.11E-17	2.02	Interferon induced protein with tetratricopeptide repeats 3
GBP1	2.39E-18	1.97	Guanylate binding protein 1
ISG15	6.50E-13	1.88	ISG15 ubiquitin like modifier
IDO1	6.95E-12	1.82	Indoleamine 2,3-dioxygenase 1
RTP4	1.65E-19	1.79	Receptor transporter protein 4
CXCL10	3.30E-12	1.78	C-X-C motif chemokine ligand 10
CASP5	1.48E-12	1.77	Caspase 5
IFI27	8.99E-07	1.76	Interferon alpha inducible protein 27
CEACAM1	1.24E-16	1.65	CEA cell adhesion molecule 1
ETV7	3.06E-16	1.65	ETS variant transcription factor 7
IFIT1	1.10E-11	1.65	Interferon induced protein with tetratricopeptide repeats 1
IFI44	5.86E-16	1.64	Interferon induced protein 44
GBP4	1.29E-20	1.56	Guanylate binding protein 4
TIMM10	5.12E-11	1.54	Translocase of inner mitochondrial membrane 10
IFI44L	3.54E-11	1.53	interferon induced protein 44 like
Down regulated genes
KLF12	1.91E-11	−1.02	Kruppel like factor 12
HOOK1	3.24E-15	−1.04	Hook microtubule tethering protein 1
OSBPL10	4.01E-10	−1.06	Oxysterol binding protein like 10
RNA5S9	6.98E-12	−1.06	RNA, 5S ribosomal 9
FAM13A	7.19E-11	−1.09	Family with sequence similarity 13 member A

Figure 1 Difference analysis and signaling pathway enrichment. (A) Principal component analysis diagram, red dots for extra-pulmonary tuberculosis, blue triangles for healthy control. (B) Heatmap was drawn for the top 25 differentially expressed genes set. (C) Differentially expressed genes set drew a volcanic map, 91 red dots represented up-regulated genes and 10 blue dots represented down-regulated genes. (D) Metascape analyzed of the first 20 significant enrichment pathways of differentially expressed genes set.

Table 2 GSEA Enrichment Analysis Results

GS Follow Link to MSigDB	NES	NOM p-val	FDR q-val
HALLMARK_INFLAMMATORY_RESPONSE	2.19	0.004	0.024
HALLMARK_INTERFERON_GAMMA_RESPONSE	2.14	0.000	0.019
HALLMARK_TNFA_SIGNALING_VIA_NFKB	2.13	0.004	0.014
HALLMARK_ALLOGRAFT_REJECTION	2.10	0.004	0.012
HALLMARK_COMPLEMENT	2.06	0.008	0.016
HALLMARK_INTERFERON_ALPHA_RESPONSE	2.04	0.000	0.016

Figure 2 Gene Set Enrichment Analysis enrichment analysis results. (A) GSEA inflammatory signaling pathway. (B) GSEA interferon-gamma signaling pathway. (C) GSEA NF-κB mediated TNFA signaling pathway. (D) GSEA allograft rejection signaling pathway. (E) GSEA complement signaling pathway. (F) GSEA interferon-alpha signaling pathway.

Table 3 MCODE Was Used to Process Data Downloaded from STRING, Specific Data of Gene Cluster

Cluster	Score	Nodes	Edges	Node IDs
1	25.462	27	331	IFI27, ISG15, IFI44L, IFI44, RTP4, PARP9, HERC5, SAMD9L, XAF1, GBP1, OAS1, CMPK2, IFI35, TRIM22, LY6E, RSAD2, CXCL10, MX1, IFIT3, IFIT1, STAT1, OASL, DDX60, EPSTI1, IFIT2, IRF7, PLSCR1
2	4	4	6	HLA-DRB5, FCGR1B, TRIM6, FCGR1A
3	3	3	3	CEACAM8, ELANE, LTF

Figure 3 The protein-protein interaction network diagrams of differential genes and key genes were visualized by Cytoscape software. (A) A protein-protein interaction network composed of 66 nodes and 509 edges and 3 main gene clusters. (B) Hub gene related protein-protein interaction network diagram.

Table 4 Tissue-Specific Expressed Genes Identified by BioGPS

System	Genes
Hematologic/immune system	ISG15, IFI44, IFI44L, RTP4, PARP9, XAF1, GBP1, OAS1, CMPK2, IFI35, TRIM22, CXCL10, IFIT3, STAT1, OASL, DDX60, IFIT2, IRF7, PLSCR1, HLA-DRB5, FCGR1B, TRIM6, FCGR1A, CEACAM8, ELANE, EPSTI1, SAMD9L, MX1, RSAD2
Respiratory system	IFI27, LY6E, LTF
Central Nervous System	IFIT1
Genitourinary system	HERC5

Table 5 Clinical Data of CNS-TB Patients

Age	Gender	Nation	The Main Symptoms	Pathological Diagnosis	Supplement
55	Male	Han nationality	frontoparietal mass for 20 days	Bilateral frontal brain regions Tuberculous granuloma	5cm*5cm subcutaneous nodule on the frontoparietal, skin-colored, soft, no tenderness, poor mobility, and fluctuating
27	Male	Minority	Repeated fever for more than 3 months with paroxysmal convulsions 3 times	The right forehead and parietal lobe Tuberculous granuloma	The patient fell repeatedly 4 times with loss of consciousness in the past 15 days. Radiographic results: intracranial multiple space-occupying lesions, larger lesions in the right forehead and parietal lobe
19	Female	Minority	Intermittent headache for more than 2 months with the right limb convulsed 3 times	Intracranial multiple caseous necrotizing Tuberculosis	Radiographic results:Multiple intracranial lesions in the right cerebellum, left occipital lobe and parietal lobe
55	Male	Minority	Intermittent headache with left limb weakness for more than 5 months	Right temporal Tuberculous granuloma	The patient felt impaired vision on the right side. Radiographic results: edema on the right temporal side, granulomatous inflammation with massive necrosis
81	Male	Minority	Intermittent headache with vision loss for 3 weeks	Left frontotemporal region Tuberculous granuloma	The patient had dizziness, headache and vomiting 1 time. Radiographic results: space-occupying lesions in the left frontotemporal area
41	Male	Minority	Intermittent headache with vomiting for 2 weeks	Cerebellar Tuberculous granuloma	The patient developed unsteady sitting and walking 7 days ago. Imaging results: cerebellar space-occupying lesions, supratentorial ventricles with dilatation and hydrocephalus

Figure 4 Hematoxylin and Eosin staining and IFIT1 typical IHC staining results and analysis. (A and B) Central nervous system tuberculosis hematoxylin and eosin (H&E) staining of lesion tissue and control tissue. (C–E) Central nervous system tuberculosis IFIT1 typical Immunohistochemistry staining. (F–H) Tuberculosis IFIT1 typical Immunohistochemistry staining. **p<0.05, The difference was statistically significant.