TISIDB

Summary
Symbol	PTGES2
Name	prostaglandin E synthase 2
Aliases	FLJ14038; C9orf15; chromosome 9 open reading frame 15; GBF-1; PGES2; mPGES-2; GATE-binding factor 1; gamma-i ......
Chromosomal Location	9q34.12
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	Golgi apparatus membrane Single-pass membrane protein ; SUBCELLULAR LOCATION: Prostaglandin E synthase 2 truncated form: Cytoplasm, perinuclear region Note=Synthesized as a Golgi membrane-bound protein, which is further cleaved into the predominant soluble truncated form. The truncated form is cytoplasmic and is enriched in the perinuclear region.
Domain	PF13417 Glutathione S-transferase
Function	Isomerase that catalyzes the conversion of PGH2 into the more stable prostaglandin E2 (PGE2).

> Gene Ontology [ TOP ]
Biological Process	GO:0001516 prostaglandin biosynthetic process GO:0006631 fatty acid metabolic process GO:0006633 fatty acid biosynthetic process GO:0006636 unsaturated fatty acid biosynthetic process GO:0006690 icosanoid metabolic process GO:0006692 prostanoid metabolic process GO:0006693 prostaglandin metabolic process GO:0016053 organic acid biosynthetic process GO:0033559 unsaturated fatty acid metabolic process GO:0044283 small molecule biosynthetic process GO:0045454 cell redox homeostasis GO:0046394 carboxylic acid biosynthetic process GO:0046456 icosanoid biosynthetic process GO:0046457 prostanoid biosynthetic process GO:0072330 monocarboxylic acid biosynthetic process
Molecular Function	GO:0009055 electron carrier activity GO:0015035 protein disulfide oxidoreductase activity GO:0015036 disulfide oxidoreductase activity GO:0016667 oxidoreductase activity, acting on a sulfur group of donors GO:0016829 lyase activity GO:0016853 isomerase activity GO:0016860 intramolecular oxidoreductase activity GO:0020037 heme binding GO:0033218 amide binding GO:0042277 peptide binding GO:0043295 glutathione binding GO:0046906 tetrapyrrole binding GO:0050220 prostaglandin-E synthase activity GO:0072341 modified amino acid binding GO:1900750 oligopeptide binding GO:1901681 sulfur compound binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00590 Arachidonic acid metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-2142753: Arachidonic acid metabolism R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-6798695: Neutrophil degranulation R-HSA-2162123: Synthesis of Prostaglandins (PG) and Thromboxanes (TX)

Summary
Symbol	PTGES2
Name	prostaglandin E synthase 2
Aliases	FLJ14038; C9orf15; chromosome 9 open reading frame 15; GBF-1; PGES2; mPGES-2; GATE-binding factor 1; gamma-i ......
Chromosomal Location	9q34.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PTGES2 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 PTGES2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19494278	Colon Carcinoma; Prostate Carcinoma	Inhibit immunity	PGDH-mediated antitumor effect was associated with attenuated tumor-induced immune suppression and substantially reduced secretion of immunosuppressive mediators and cytokines such as PGE(2), IL-10, IL-13, and IL-6 by intratumoral CD11b cells. We show also that introduction of 15-PGDH gene in tumor tissue is sufficient to redirect the differentiation of intratumoral CD11b cells from immunosuppressive M2-oriented F4/80(+) tumor-associated macrophages (TAM) into M1-oriented CD11c(+) MHC class II-positive myeloid APCs.
16778191	Breast Carcinoma	Inhibit immunity (T cell function)	Different progression of tumor xenografts between mucin-producing and mucin-non-producing mammary adenocarcinoma-bearing mice. tumor formation by using mucin-producing (TA3-Ha) and mucin-non-producing (TA3-St) cloned variants of mouse mammary adenocarcinomas. IFN-gamma-producing CD4 T cells in spleens obtained from TA3-Ha tumor-bearing mice were significantly reduced compared with TA3-St tumor-bearing mice, suggesting that mucins cause PGE2-mediated immune suppression.
22333315	Breast Carcinoma	Inhibit immunity (T and NK cell function); immunotherapy target	In murine breast cancer models, the two interferon-gamma (IFN-γ) inducible chemokines and CXC-chemokine receptor 3 (CXCR3) receptor ligands, monokine induced by γ-interferon (CXCL9) and interferon-γ-inducible protein-10 (CXCL10) impair tumor growth and metastasis formation through recruitment of natural killer (NK) cells and tumor-suppressive T lymphocytes. PGE2 impairs IFN-γ mediated CXCL9 and CXCL10 release from MCF-7 and MDA-MB 231 cells, and inhibition of endogenous cyclooxygenases by indomethacin or ASA correspondingly increases this secretion. Suppressing endogenous PGE2 synthesis by cyclooxygenase inhibition increases CXCL9 and CXCL10 release from breast cancer cells and is therefore a pharmacologic candidate to enhance intratumoral immune infiltration.

Summary
Symbol	PTGES2
Name	prostaglandin E synthase 2
Aliases	FLJ14038; C9orf15; chromosome 9 open reading frame 15; GBF-1; PGES2; mPGES-2; GATE-binding factor 1; gamma-i ......
Chromosomal Location	9q34.12
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 PTGES2 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	PTGES2
Name	prostaglandin E synthase 2
Aliases	FLJ14038; C9orf15; chromosome 9 open reading frame 15; GBF-1; PGES2; mPGES-2; GATE-binding factor 1; gamma-i ......
Chromosomal Location	9q34.12
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 PTGES2 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	-0.239	0.519
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.386	0.866
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.139	0.939
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.305	0.366
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.261	0.883
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.369	0.88
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.206	0.533
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.046	0.972
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.372	0.803
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.075	0.959
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	-0.02	0.993
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.112	0.16

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PTGES2 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	5.9	-5.9	0.447
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	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
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	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	PTGES2
Name	prostaglandin E synthase 2
Aliases	FLJ14038; C9orf15; chromosome 9 open reading frame 15; GBF-1; PGES2; mPGES-2; GATE-binding factor 1; gamma-i ......
Chromosomal Location	9q34.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PTGES2. 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	PTGES2
Name	prostaglandin E synthase 2
Aliases	FLJ14038; C9orf15; chromosome 9 open reading frame 15; GBF-1; PGES2; mPGES-2; GATE-binding factor 1; gamma-i ......
Chromosomal Location	9q34.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PTGES2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PTGES2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PTGES2
Name	prostaglandin E synthase 2
Aliases	FLJ14038; C9orf15; chromosome 9 open reading frame 15; GBF-1; PGES2; mPGES-2; GATE-binding factor 1; gamma-i ......
Chromosomal Location	9q34.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PTGES2. 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	PTGES2
Name	prostaglandin E synthase 2
Aliases	FLJ14038; C9orf15; chromosome 9 open reading frame 15; GBF-1; PGES2; mPGES-2; GATE-binding factor 1; gamma-i ......
Chromosomal Location	9q34.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PTGES2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PTGES2
Name	prostaglandin E synthase 2
Aliases	FLJ14038; C9orf15; chromosome 9 open reading frame 15; GBF-1; PGES2; mPGES-2; GATE-binding factor 1; gamma-i ......
Chromosomal Location	9q34.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PTGES2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PTGES2
Name	prostaglandin E synthase 2
Aliases	FLJ14038; C9orf15; chromosome 9 open reading frame 15; GBF-1; PGES2; mPGES-2; GATE-binding factor 1; gamma-i ......
Chromosomal Location	9q34.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PTGES2 collected from DrugBank database.

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

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