TISIDB

Summary
Symbol	MSLN
Name	mesothelin
Aliases	MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location	16p13.3
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	Cell membrane; Lipid-anchor, GPI-anchor. Golgi apparatus.; SUBCELLULAR LOCATION: Megakaryocyte-potentiating factor: Secreted.; SUBCELLULAR LOCATION: Isoform 3: Secreted.
Domain	PF06060 Pre-pro-megakaryocyte potentiating factor precursor (Mesothelin)
Function	Membrane-anchored forms may play a role in cellular adhesion.; FUNCTION: Megakaryocyte-potentiating factor (MPF) potentiates megakaryocyte colony formation in vitro.

> Gene Ontology [ TOP ]
Biological Process	GO:0007160 cell-matrix adhesion GO:0031016 pancreas development GO:0031589 cell-substrate adhesion
Molecular Function	-
Cellular Component	GO:0031225 anchored component of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-392499: Metabolism of proteins R-HSA-163125: Post-translational modification R-HSA-597592: Post-translational protein modification

Summary
Symbol	MSLN
Name	mesothelin
Aliases	MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location	16p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MSLN 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

[ TOP ]

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

PMID	Cancer type	Relation to immunity	Evidence sentences
18281514	Pancreatic Carcinoma	Inhibit immunity (T cell function); immunotherapy target	We have shown that mesothelin expression was higher in human pancreatic cancer cells than in human pancreatic duct epithelial cells, and mesothelin mRNA was substantially overexpressed in 18 of 21 (86%) clinical pancreatic adenocarcinoma specimens when compared with the surrounding normal tissues. The increases in mesothelin-specific antibodies and CTL activity and the decrease in regulatory T cells correlated with reduced tumor progression and prolonged survival.
22418702	Triple-negative breast carcinoma	Promote immunity (T cell function); essential for immunotherapy	MSLN is expressed in majority of triple negative breast carcinoma, while very rare in positive breast cancer. Application of CAR T modified to express MSLN-specific chimeric antibody receptor exert higher anti-tumor cytotoxicity than non-transduced T cells, suggesting that MSLN is a novel immunotherapy target. Therefore, we screened 99 primary breast cancer samples by immunohistochemistry analysis using formalin-fixed paraffin-embedded archival tumor tissues and confirmed that mesothelin was overexpressed in the majority of TNBC (67 %) but only rarely in <5 % ER(+) or Her2-neu(+) breast cancer, respectively. A significantly higher anti-tumor cytotoxicity by mesoCAR T cells was observed (31.7 vs. 8.7 %, p < 0.001). Our results suggest that mesothelin has promise as a novel immunotherapy target for TNBC for which effective targeted therapy is lacking to date.
23183537	Cervical carcinoma	Inhibit immunity	The tumor-homing module is comprised of a single-chain variable fragment (scFv) that specifically binds to mesothelin (Meso), which is commonly overexpressed in human cancers, including ovarian tumors. We show that our therapeutic protein specifically loaded antigenic epitope onto the surface of mesothelin-expressing tumor cells, rendering tumors susceptible to antigen-specific cytotoxic CD8(+) T lymphocytes (CTL)-mediated killing in vitro and in vivo. Our findings have important implications for bypassing immune tolerance to enhance cancer immunotherapy.
29596890	ovarian carcinoma; Pancreatic ductal adenocarcinoma; mesothelioma	Promote immunity	The results indicate that an MSLN-specific DNA vaccine combined with immuno-modulators may be an effective immunotherapeutic strategy to control MSLN-expressing tumors including ovarian and pancreastic cancers, and malignant mesothelioma.
27863199	Malignant Mesothelioma; Pancreatic Adenocarcinoma; Ovarian Adenocarcinoma; Lung Adenocarcinoma	Promote immunity	Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable.
20635390	Mesothelioma; Ovarian Carcinoma; Lung Adenocarcinoma; Pancreatic Carcinoma	Inhibit immunity	Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of mesothelioma, ovarian cancer and other malignant tumors. The interaction between mesothelin and CA125 (also called MUC16) may facilitate the implantation and metastasis of tumors in the peritoneal cavity.

Summary
Symbol	MSLN
Name	mesothelin
Aliases	MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location	16p13.3
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

[ TOP ]

Statistical results of MSLN 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	MSLN
Name	mesothelin
Aliases	MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location	16p13.3
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

[ TOP ]

Points in the above scatter plot represent the expression difference of MSLN 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	0.216	0.346
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.264	0.608
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.567	0.171
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	1.745	0.0882
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	2.656	0.127
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.58	0.757
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.768	0.297
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.22	0.404
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.349	0.833
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.435	0.707
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	-0.435	0.776
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.006	0.989

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of MSLN 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	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
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	1.4	-1.4	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	1.7	-1.7	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	10.5	3.7	6.8	0.393
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	0	13.6	0.279
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	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	MSLN
Name	mesothelin
Aliases	MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location	16p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MSLN. 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	MSLN
Name	mesothelin
Aliases	MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location	16p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MSLN. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MSLN. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MSLN
Name	mesothelin
Aliases	MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location	16p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MSLN. 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	MSLN
Name	mesothelin
Aliases	MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location	16p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MSLN expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MSLN
Name	mesothelin
Aliases	MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location	16p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MSLN and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MSLN
Name	mesothelin
Aliases	MPF; CAK1 antigen; megakaryocyte potentiating factor; pre-pro-megakaryocyte-potentiating factor; soluble MPF ......
Chromosomal Location	16p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MSLN collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting MSLN.

ID	Name	Drug Type	Targets	#Targets
DB12845	Amatuximab	Biotech	MSLN	1

Browse MSLN