TISIDB

Summary
Symbol	HPGD
Name	hydroxyprostaglandin dehydrogenase 15-(NAD)
Aliases	SDR36C1; short chain dehydrogenase/reductase family 36C, member 1; 15-PGDH; PGDH1; PHOAR1; NAD+-dependent 15 ......
Chromosomal Location	4q34-q35
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	Cytoplasm.
Domain	PF00106 short chain dehydrogenase
Function	Prostaglandin inactivation. Contributes to the regulation of events that are under the control of prostaglandin levels. Catalyzes the NAD-dependent dehydrogenation of lipoxin A4 to form 15-oxo-lipoxin A4. Inhibits in vivo proliferation of colon cancer cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0006631 fatty acid metabolic process GO:0006690 icosanoid metabolic process GO:0006692 prostanoid metabolic process GO:0006693 prostaglandin metabolic process GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007179 transforming growth factor beta receptor signaling pathway GO:0007292 female gamete generation GO:0007565 female pregnancy GO:0007567 parturition GO:0019372 lipoxygenase pathway GO:0030728 ovulation GO:0033559 unsaturated fatty acid metabolic process GO:0044706 multi-multicellular organism process GO:0045786 negative regulation of cell cycle GO:0048514 blood vessel morphogenesis GO:0048844 artery morphogenesis GO:0060840 artery development GO:0070493 thrombin receptor signaling pathway GO:0071559 response to transforming growth factor beta GO:0071560 cellular response to transforming growth factor beta stimulus GO:0097070 ductus arteriosus closure GO:1901568 fatty acid derivative metabolic process GO:2001300 lipoxin metabolic process
Molecular Function	GO:0004953 icosanoid receptor activity GO:0004954 prostanoid receptor activity GO:0004955 prostaglandin receptor activity GO:0004957 prostaglandin E receptor activity GO:0016404 15-hydroxyprostaglandin dehydrogenase (NAD+) activity GO:0016614 oxidoreductase activity, acting on CH-OH group of donors GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor GO:0048037 cofactor binding GO:0050662 coenzyme binding GO:0051287 NAD binding GO:0070403 NAD+ binding
Cellular Component	GO:0016323 basolateral plasma membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-2142753: Arachidonic acid metabolism R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-2142700: Synthesis of Lipoxins (LX) R-HSA-2162123: Synthesis of Prostaglandins (PG) and Thromboxanes (TX)

Summary
Symbol	HPGD
Name	hydroxyprostaglandin dehydrogenase 15-(NAD)
Aliases	SDR36C1; short chain dehydrogenase/reductase family 36C, member 1; 15-PGDH; PGDH1; PHOAR1; NAD+-dependent 15 ......
Chromosomal Location	4q34-q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HPGD 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 HPGD and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19494278	Colon Carcinoma; Prostate Carcinoma	Promote 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.
19887544	Breast Carcinoma; Colon Carcinoma	Promote immunity	Preclinical and clinical evidence shows that cyclooxygenase-2 (Cox-2)-mediated prostaglandin E(2) (PGE(2)) overexpression plays an important role in tumor growth, metastasis, and immunosuppression. It has been shown that expression of NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key enzyme responsible for PGE(2) inactivation, is suppressed in the majority of cancers, including breast and colon carcinoma. The in vitro study showed that Ad-mediated 15-PGDH expression significantly decreased proliferation and migration of cancer cells. Animal breast and colon tumor therapy studies showed that 15-PGDH gene therapy produced a significant delay in 2LMP and LS174T tumor growth. Combined therapy using 15-PGDH and anti-VEGF antibody (bevacizumab) significantly increased inhibition of growth of LS174T tumor xenografts in comparison with agents alone.

Summary
Symbol	HPGD
Name	hydroxyprostaglandin dehydrogenase 15-(NAD)
Aliases	SDR36C1; short chain dehydrogenase/reductase family 36C, member 1; 15-PGDH; PGDH1; PHOAR1; NAD+-dependent 15 ......
Chromosomal Location	4q34-q35
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 HPGD 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	HPGD
Name	hydroxyprostaglandin dehydrogenase 15-(NAD)
Aliases	SDR36C1; short chain dehydrogenase/reductase family 36C, member 1; 15-PGDH; PGDH1; PHOAR1; NAD+-dependent 15 ......
Chromosomal Location	4q34-q35
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 HPGD 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	0.934	0.29
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.112	0.581
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.824	0.554
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.858	0.327
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.526	0.775
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.26	0.498
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.981	0.171
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.634	0.275
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.025	0.99
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.249	0.31
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	2.939	0.0547
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.251	0.498

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HPGD 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	1.4	2.3	0.469
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	1.7	2	0.532
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	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	HPGD
Name	hydroxyprostaglandin dehydrogenase 15-(NAD)
Aliases	SDR36C1; short chain dehydrogenase/reductase family 36C, member 1; 15-PGDH; PGDH1; PHOAR1; NAD+-dependent 15 ......
Chromosomal Location	4q34-q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HPGD. 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	HPGD
Name	hydroxyprostaglandin dehydrogenase 15-(NAD)
Aliases	SDR36C1; short chain dehydrogenase/reductase family 36C, member 1; 15-PGDH; PGDH1; PHOAR1; NAD+-dependent 15 ......
Chromosomal Location	4q34-q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HPGD. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HPGD. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HPGD
Name	hydroxyprostaglandin dehydrogenase 15-(NAD)
Aliases	SDR36C1; short chain dehydrogenase/reductase family 36C, member 1; 15-PGDH; PGDH1; PHOAR1; NAD+-dependent 15 ......
Chromosomal Location	4q34-q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HPGD. 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	HPGD
Name	hydroxyprostaglandin dehydrogenase 15-(NAD)
Aliases	SDR36C1; short chain dehydrogenase/reductase family 36C, member 1; 15-PGDH; PGDH1; PHOAR1; NAD+-dependent 15 ......
Chromosomal Location	4q34-q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HPGD expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HPGD
Name	hydroxyprostaglandin dehydrogenase 15-(NAD)
Aliases	SDR36C1; short chain dehydrogenase/reductase family 36C, member 1; 15-PGDH; PGDH1; PHOAR1; NAD+-dependent 15 ......
Chromosomal Location	4q34-q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HPGD and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HPGD
Name	hydroxyprostaglandin dehydrogenase 15-(NAD)
Aliases	SDR36C1; short chain dehydrogenase/reductase family 36C, member 1; 15-PGDH; PGDH1; PHOAR1; NAD+-dependent 15 ......
Chromosomal Location	4q34-q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HPGD collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting HPGD.

ID	Name	Drug Type	Targets	#Targets
DB00157	NADH	Small Molecule	AASS, ACADS, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH7, AKR1B1, AKR1C1 ......	144

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