TISIDB

Summary
Symbol	IGFBP7
Name	insulin-like growth factor binding protein 7
Aliases	MAC25; IGFBP-7; FSTL2; AGM; IBP-7; IGFBP-7v; IGFBPRP1; RAMSVPS; IGF-binding protein 7; IGFBP-rP1; PGI2-stimu ......
Chromosomal Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Secreted.
Domain	PF00219 Insulin-like growth factor binding protein PF07648 Kazal-type serine protease inhibitor domain
Function	Binds IGF-I and IGF-II with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion.

> Gene Ontology [ TOP ]
Biological Process	GO:0001101 response to acid chemical GO:0001558 regulation of cell growth GO:0006694 steroid biosynthetic process GO:0007565 female pregnancy GO:0007566 embryo implantation GO:0008202 steroid metabolic process GO:0009266 response to temperature stimulus GO:0009408 response to heat GO:0016049 cell growth GO:0019216 regulation of lipid metabolic process GO:0019218 regulation of steroid metabolic process GO:0031960 response to corticosteroid GO:0032526 response to retinoic acid GO:0044706 multi-multicellular organism process GO:0046890 regulation of lipid biosynthetic process GO:0048545 response to steroid hormone GO:0050810 regulation of steroid biosynthetic process GO:0051384 response to glucocorticoid GO:0051414 response to cortisol GO:1901654 response to ketone
Molecular Function	GO:0005520 insulin-like growth factor binding GO:0019838 growth factor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-2559583: Cellular Senescence R-HSA-2262752: Cellular responses to stress R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP)

Summary
Symbol	IGFBP7
Name	insulin-like growth factor binding protein 7
Aliases	MAC25; IGFBP-7; FSTL2; AGM; IBP-7; IGFBP-7v; IGFBPRP1; RAMSVPS; IGF-binding protein 7; IGFBP-rP1; PGI2-stimu ......
Chromosomal Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IGFBP7 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between IGFBP7 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28619711	Hepatocellular Carcinoma	Promote immunity	IGFBP7 Deletion Promotes Hepatocellular Carcinoma. IGFBP7 abrogates tumors by inhibiting angiogenesis and inducing cancer-specific senescence and apoptosis. Here, we report that Igfbp7-deficient mice exhibit constitutively active IGF signaling, presenting with proinflammatory and immunosuppressive microenvironments and spontaneous liver and lung tumors occurring with increased incidence in carcinogen-treated subjects. Igfbp7 deletion increased proliferation and decreased senescence of hepatocytes and mouse embryonic fibroblasts, effects that were blocked by treatment with IGF1 receptor inhibitor.

Summary
Symbol	IGFBP7
Name	insulin-like growth factor binding protein 7
Aliases	MAC25; IGFBP-7; FSTL2; AGM; IBP-7; IGFBP-7v; IGFBPRP1; RAMSVPS; IGF-binding protein 7; IGFBP-rP1; PGI2-stimu ......
Chromosomal Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of IGFBP7 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	IGFBP7
Name	insulin-like growth factor binding protein 7
Aliases	MAC25; IGFBP-7; FSTL2; AGM; IBP-7; IGFBP-7v; IGFBPRP1; RAMSVPS; IGF-binding protein 7; IGFBP-rP1; PGI2-stimu ......
Chromosomal Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of IGFBP7 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.664	0.0632
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.57	0.889
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.741	0.811
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.26	0.518
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.22	0.936
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.312	0.928
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.189	0.738
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.101	0.963
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.497	0.837
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.008	0.74
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.322	0.777
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.507	0.000385

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IGFBP7 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	IGFBP7
Name	insulin-like growth factor binding protein 7
Aliases	MAC25; IGFBP-7; FSTL2; AGM; IBP-7; IGFBP-7v; IGFBPRP1; RAMSVPS; IGF-binding protein 7; IGFBP-rP1; PGI2-stimu ......
Chromosomal Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IGFBP7. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	IGFBP7
Name	insulin-like growth factor binding protein 7
Aliases	MAC25; IGFBP-7; FSTL2; AGM; IBP-7; IGFBP-7v; IGFBPRP1; RAMSVPS; IGF-binding protein 7; IGFBP-rP1; PGI2-stimu ......
Chromosomal Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IGFBP7. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IGFBP7. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IGFBP7
Name	insulin-like growth factor binding protein 7
Aliases	MAC25; IGFBP-7; FSTL2; AGM; IBP-7; IGFBP-7v; IGFBPRP1; RAMSVPS; IGF-binding protein 7; IGFBP-rP1; PGI2-stimu ......
Chromosomal Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IGFBP7. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	IGFBP7
Name	insulin-like growth factor binding protein 7
Aliases	MAC25; IGFBP-7; FSTL2; AGM; IBP-7; IGFBP-7v; IGFBPRP1; RAMSVPS; IGF-binding protein 7; IGFBP-rP1; PGI2-stimu ......
Chromosomal Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IGFBP7 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IGFBP7
Name	insulin-like growth factor binding protein 7
Aliases	MAC25; IGFBP-7; FSTL2; AGM; IBP-7; IGFBP-7v; IGFBPRP1; RAMSVPS; IGF-binding protein 7; IGFBP-rP1; PGI2-stimu ......
Chromosomal Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IGFBP7 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IGFBP7
Name	insulin-like growth factor binding protein 7
Aliases	MAC25; IGFBP-7; FSTL2; AGM; IBP-7; IGFBP-7v; IGFBPRP1; RAMSVPS; IGF-binding protein 7; IGFBP-rP1; PGI2-stimu ......
Chromosomal Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IGFBP7 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting IGFBP7.

ID	Name	Drug Type	Targets	#Targets
DB00030	Insulin Human	Biotech	CPE, CTSD, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV, PCSK1, PCSK2, RB1, ......	12
DB00071	Insulin Pork	Biotech	CPE, CTSD, HLA-DQA2, HLA-DQB1, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV ......	14

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