TISIDB

Summary
Symbol	SERPINB4
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 4
Aliases	PI11; LEUPIN; SCCA-2; squamous cell carcinoma antigen 2; SCCA2; serine (or cysteine) proteinase inhibitor, c ......
Chromosomal Location	18q21.33
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 Note=Seems to also be secreted in plasma by cancerous cells but at a low level.
Domain	PF00079 Serpin (serine protease inhibitor)
Function	May act as a protease inhibitor to modulate the host immune response against tumor cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0001906 cell killing GO:0001909 leukocyte mediated cytotoxicity GO:0001910 regulation of leukocyte mediated cytotoxicity GO:0001911 negative regulation of leukocyte mediated cytotoxicity GO:0002228 natural killer cell mediated immunity GO:0002443 leukocyte mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002683 negative regulation of immune system process GO:0002697 regulation of immune effector process GO:0002698 negative regulation of immune effector process GO:0002703 regulation of leukocyte mediated immunity GO:0002704 negative regulation of leukocyte mediated immunity GO:0002706 regulation of lymphocyte mediated immunity GO:0002707 negative regulation of lymphocyte mediated immunity GO:0002715 regulation of natural killer cell mediated immunity GO:0002716 negative regulation of natural killer cell mediated immunity GO:0010466 negative regulation of peptidase activity GO:0010951 negative regulation of endopeptidase activity GO:0031341 regulation of cell killing GO:0031342 negative regulation of cell killing GO:0031348 negative regulation of defense response GO:0042267 natural killer cell mediated cytotoxicity GO:0042269 regulation of natural killer cell mediated cytotoxicity GO:0042270 protection from natural killer cell mediated cytotoxicity GO:0045088 regulation of innate immune response GO:0045824 negative regulation of innate immune response GO:0045861 negative regulation of proteolysis GO:0045953 negative regulation of natural killer cell mediated cytotoxicity GO:0050777 negative regulation of immune response GO:0051346 negative regulation of hydrolase activity GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity
Molecular Function	GO:0002020 protease binding GO:0004857 enzyme inhibitor activity GO:0004866 endopeptidase inhibitor activity GO:0004867 serine-type endopeptidase inhibitor activity GO:0030414 peptidase inhibitor activity GO:0061134 peptidase regulator activity GO:0061135 endopeptidase regulator activity
Cellular Component	-

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

Summary
Symbol	SERPINB4
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 4
Aliases	PI11; LEUPIN; SCCA-2; squamous cell carcinoma antigen 2; SCCA2; serine (or cysteine) proteinase inhibitor, c ......
Chromosomal Location	18q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SERPINB4 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 SERPINB4 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27668655	Melanoma	Promote immunity (T cell function); essential for immunotherapy	Here we show that somatic mutations in SERPINB3 and SERPINB4 are associated with survival after anti-CTLA4 immunotherapy in two independent cohorts of patients with melanoma. Interestingly, serpins are homologs of the well-known ovalbumin antigen and are associated with autoimmunity.

Summary
Symbol	SERPINB4
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 4
Aliases	PI11; LEUPIN; SCCA-2; squamous cell carcinoma antigen 2; SCCA2; serine (or cysteine) proteinase inhibitor, c ......
Chromosomal Location	18q21.33
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 SERPINB4 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	SERPINB4
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 4
Aliases	PI11; LEUPIN; SCCA-2; squamous cell carcinoma antigen 2; SCCA2; serine (or cysteine) proteinase inhibitor, c ......
Chromosomal Location	18q21.33
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 SERPINB4 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	0.866	0.35
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.138	0.925
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.618	0.199
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.745	0.39
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.276	0.34
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.082	0.956
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.959	0.345
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-1.381	0.432
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.435	0.825
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.324	0.564
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	-0.324	0.683
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.565	0.333

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SERPINB4 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	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	4.8	17.6	-12.8	0.307
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	7.7	27.3	-19.6	0.3
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	5.3	3.7	1.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	7.7	1.4	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	SERPINB4
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 4
Aliases	PI11; LEUPIN; SCCA-2; squamous cell carcinoma antigen 2; SCCA2; serine (or cysteine) proteinase inhibitor, c ......
Chromosomal Location	18q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SERPINB4. 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	SERPINB4
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 4
Aliases	PI11; LEUPIN; SCCA-2; squamous cell carcinoma antigen 2; SCCA2; serine (or cysteine) proteinase inhibitor, c ......
Chromosomal Location	18q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SERPINB4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SERPINB4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SERPINB4
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 4
Aliases	PI11; LEUPIN; SCCA-2; squamous cell carcinoma antigen 2; SCCA2; serine (or cysteine) proteinase inhibitor, c ......
Chromosomal Location	18q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SERPINB4. 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	SERPINB4
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 4
Aliases	PI11; LEUPIN; SCCA-2; squamous cell carcinoma antigen 2; SCCA2; serine (or cysteine) proteinase inhibitor, c ......
Chromosomal Location	18q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SERPINB4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SERPINB4
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 4
Aliases	PI11; LEUPIN; SCCA-2; squamous cell carcinoma antigen 2; SCCA2; serine (or cysteine) proteinase inhibitor, c ......
Chromosomal Location	18q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SERPINB4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SERPINB4
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 4
Aliases	PI11; LEUPIN; SCCA-2; squamous cell carcinoma antigen 2; SCCA2; serine (or cysteine) proteinase inhibitor, c ......
Chromosomal Location	18q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SERPINB4 collected from DrugBank database.

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

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