TISIDB

Summary
Symbol	GDF15
Name	growth differentiation factor 15
Aliases	PLAB; NAG-1; PTGFB; prostate differentiation factor; GDF-15; NRG-1; NSAID (nonsteroidal anti-inflammatory dr ......
Chromosomal Location	19p13.11
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	PF00019 Transforming growth factor beta like domain
Function	Regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:23468844, PubMed:29046435). Binds to its receptor, GFRAL, and activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099). It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which contitutes part of the 'emergency circuit' that shapes feeding responses to stressful conditions (PubMed:28953886). On hepatocytes, inhibits growth hormone signaling (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000768 syncytium formation by plasma membrane fusion GO:0006949 syncytium formation GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007179 transforming growth factor beta receptor signaling pathway GO:0007520 myoblast fusion GO:0010830 regulation of myotube differentiation GO:0010831 positive regulation of myotube differentiation GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0014902 myotube differentiation GO:0042692 muscle cell differentiation GO:0051146 striated muscle cell differentiation GO:0051147 regulation of muscle cell differentiation GO:0051149 positive regulation of muscle cell differentiation GO:0051153 regulation of striated muscle cell differentiation GO:0051155 positive regulation of striated muscle cell differentiation GO:0060142 regulation of syncytium formation by plasma membrane fusion GO:0060143 positive regulation of syncytium formation by plasma membrane fusion GO:0060389 pathway-restricted SMAD protein phosphorylation GO:0060393 regulation of pathway-restricted SMAD protein phosphorylation GO:0060395 SMAD protein signal transduction GO:0071559 response to transforming growth factor beta GO:0071560 cellular response to transforming growth factor beta stimulus GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GO:0090100 positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GO:1901739 regulation of myoblast fusion GO:1901741 positive regulation of myoblast fusion
Molecular Function	GO:0005125 cytokine activity GO:0005126 cytokine receptor binding GO:0005160 transforming growth factor beta receptor binding GO:0008083 growth factor activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	GDF15
Name	growth differentiation factor 15
Aliases	PLAB; NAG-1; PTGFB; prostate differentiation factor; GDF-15; NRG-1; NSAID (nonsteroidal anti-inflammatory dr ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GDF15 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 GDF15 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28891811	Pancreatic Carcinoma	Inhibit immunity	In vitro, tumor-derived GDF-15 signals in macrophages to suppress their proapoptotic activity by inhibiting TNF and nitric oxide (NO) production. In vivo, depletion of GDF-15 in Ras-driven tumor xenografts and in an orthotopic model of pancreatic cancer delayed tumor development.
20534737	Malignant Glioma	Inhibit immunity	GDF-15 contributes to proliferation and immune escape of malignant gliomas. The high expression of GDF-15 in tumor tissue translates into elevated GDF-15 serum levels in glioblastoma patients compared with healthy controls. Silencing of GDF-15 by RNA interference reduces the proliferation of malignant glioma cells. Although previous studies focusing on ectopic overexpression of GDF-15 have proposed unclear or antitumorigenic effects of GDF-15 in glioma cells, we here show that GDF-15 at endogenous levels contributes to proliferation and immune escape of malignant gliomas in an immunocompetent host.

Summary
Symbol	GDF15
Name	growth differentiation factor 15
Aliases	PLAB; NAG-1; PTGFB; prostate differentiation factor; GDF-15; NRG-1; NSAID (nonsteroidal anti-inflammatory dr ......
Chromosomal Location	19p13.11
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 GDF15 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	GDF15
Name	growth differentiation factor 15
Aliases	PLAB; NAG-1; PTGFB; prostate differentiation factor; GDF-15; NRG-1; NSAID (nonsteroidal anti-inflammatory dr ......
Chromosomal Location	19p13.11
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 GDF15 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	0.85	0.356
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.045	0.784
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.704	0.809
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.54	0.483
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.755	0.723
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.263	0.917
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.242	0.761
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-1.197	0.48
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.745	0.698
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.041	0.982
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	-0.485	0.849
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.021	0.936

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of GDF15 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	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	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	3.7	0	3.7	0.27
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	3.7	0	3.7	0.314
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	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	3.7	-3.7	0.415
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	7.1	-7.1	0.467
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	GDF15
Name	growth differentiation factor 15
Aliases	PLAB; NAG-1; PTGFB; prostate differentiation factor; GDF-15; NRG-1; NSAID (nonsteroidal anti-inflammatory dr ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GDF15. 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	GDF15
Name	growth differentiation factor 15
Aliases	PLAB; NAG-1; PTGFB; prostate differentiation factor; GDF-15; NRG-1; NSAID (nonsteroidal anti-inflammatory dr ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GDF15. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GDF15. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GDF15
Name	growth differentiation factor 15
Aliases	PLAB; NAG-1; PTGFB; prostate differentiation factor; GDF-15; NRG-1; NSAID (nonsteroidal anti-inflammatory dr ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GDF15. 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	GDF15
Name	growth differentiation factor 15
Aliases	PLAB; NAG-1; PTGFB; prostate differentiation factor; GDF-15; NRG-1; NSAID (nonsteroidal anti-inflammatory dr ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GDF15 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GDF15
Name	growth differentiation factor 15
Aliases	PLAB; NAG-1; PTGFB; prostate differentiation factor; GDF-15; NRG-1; NSAID (nonsteroidal anti-inflammatory dr ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GDF15 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GDF15
Name	growth differentiation factor 15
Aliases	PLAB; NAG-1; PTGFB; prostate differentiation factor; GDF-15; NRG-1; NSAID (nonsteroidal anti-inflammatory dr ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GDF15 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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