TISIDB

Summary
Symbol	EGF
Name	epidermal growth factor
Aliases	epidermal growth factor (beta-urogastrone); HOMG4; URG; beta-urogastrone; Pro-epidermal growth factor
Chromosomal Location	4q25
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	Membrane; Single-pass type I membrane protein.
Domain	PF00008 EGF-like domain PF07645 Calcium-binding EGF domain PF00058 Low-density lipoprotein receptor repeat class B
Function	EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6. Can induce neurite outgrowth in motoneurons of the pond snail Lymnaea stagnalis in vitro (PubMed:10964941).

> Gene Ontology [ TOP ]
Biological Process	GO:0000186 activation of MAPKK activity GO:0000187 activation of MAPK activity GO:0000271 polysaccharide biosynthetic process GO:0001525 angiogenesis GO:0001763 morphogenesis of a branching structure GO:0002576 platelet degranulation GO:0003002 regionalization GO:0005976 polysaccharide metabolic process GO:0006022 aminoglycan metabolic process GO:0006023 aminoglycan biosynthetic process GO:0006024 glycosaminoglycan biosynthetic process GO:0006109 regulation of carbohydrate metabolic process GO:0006260 DNA replication GO:0006606 protein import into nucleus GO:0006644 phospholipid metabolic process GO:0006650 glycerophospholipid metabolic process GO:0006816 calcium ion transport GO:0006869 lipid transport GO:0006887 exocytosis GO:0006913 nucleocytoplasmic transport GO:0007067 mitotic nuclear division GO:0007088 regulation of mitotic nuclear division GO:0007171 activation of transmembrane receptor protein tyrosine kinase activity GO:0007173 epidermal growth factor receptor signaling pathway GO:0007176 regulation of epidermal growth factor-activated receptor activity GO:0007259 JAK-STAT cascade GO:0007262 STAT protein import into nucleus GO:0007346 regulation of mitotic cell cycle GO:0007389 pattern specification process GO:0009798 axis specification GO:0009894 regulation of catabolic process GO:0009896 positive regulation of catabolic process GO:0009950 dorsal/ventral axis specification GO:0009953 dorsal/ventral pattern formation GO:0010469 regulation of receptor activity GO:0010799 regulation of peptidyl-threonine phosphorylation GO:0010800 positive regulation of peptidyl-threonine phosphorylation GO:0010874 regulation of cholesterol efflux GO:0010876 lipid localization GO:0010959 regulation of metal ion transport GO:0014065 phosphatidylinositol 3-kinase signaling GO:0014066 regulation of phosphatidylinositol 3-kinase signaling GO:0015850 organic hydroxy compound transport GO:0015918 sterol transport GO:0016051 carbohydrate biosynthetic process GO:0016055 Wnt signaling pathway GO:0017038 protein import GO:0018107 peptidyl-threonine phosphorylation GO:0018108 peptidyl-tyrosine phosphorylation GO:0018210 peptidyl-threonine modification GO:0018212 peptidyl-tyrosine modification GO:0021534 cell proliferation in hindbrain GO:0021924 cell proliferation in external granule layer GO:0021930 cerebellar granule cell precursor proliferation GO:0021936 regulation of cerebellar granule cell precursor proliferation GO:0021940 positive regulation of cerebellar granule cell precursor proliferation GO:0030203 glycosaminoglycan metabolic process GO:0030212 hyaluronan metabolic process GO:0030213 hyaluronan biosynthetic process GO:0030258 lipid modification GO:0030301 cholesterol transport GO:0030879 mammary gland development GO:0030902 hindbrain development GO:0031329 regulation of cellular catabolic process GO:0031331 positive regulation of cellular catabolic process GO:0031396 regulation of protein ubiquitination GO:0031398 positive regulation of protein ubiquitination GO:0032147 activation of protein kinase activity GO:0032368 regulation of lipid transport GO:0032369 negative regulation of lipid transport GO:0032371 regulation of sterol transport GO:0032372 negative regulation of sterol transport GO:0032374 regulation of cholesterol transport GO:0032375 negative regulation of cholesterol transport GO:0032386 regulation of intracellular transport GO:0032388 positive regulation of intracellular transport GO:0032881 regulation of polysaccharide metabolic process GO:0032885 regulation of polysaccharide biosynthetic process GO:0033157 regulation of intracellular protein transport GO:0033344 cholesterol efflux GO:0033674 positive regulation of kinase activity GO:0034394 protein localization to cell surface GO:0034504 protein localization to nucleus GO:0035239 tube morphogenesis GO:0035411 catenin import into nucleus GO:0035412 regulation of catenin import into nucleus GO:0035413 positive regulation of catenin import into nucleus GO:0038127 ERBB signaling pathway GO:0038128 ERBB2 signaling pathway GO:0042058 regulation of epidermal growth factor receptor signaling pathway GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway GO:0042176 regulation of protein catabolic process GO:0042306 regulation of protein import into nucleus GO:0042307 positive regulation of protein import into nucleus GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:0043255 regulation of carbohydrate biosynthetic process GO:0043388 positive regulation of DNA binding GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0044332 Wnt signaling pathway involved in dorsal/ventral axis specification GO:0044723 single-organism carbohydrate metabolic process GO:0044744 protein targeting to nucleus GO:0045055 regulated exocytosis GO:0045732 positive regulation of protein catabolic process GO:0045741 positive regulation of epidermal growth factor-activated receptor activity GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway GO:0045787 positive regulation of cell cycle GO:0045840 positive regulation of mitotic nuclear division GO:0045860 positive regulation of protein kinase activity GO:0045862 positive regulation of proteolysis GO:0045913 positive regulation of carbohydrate metabolic process GO:0045931 positive regulation of mitotic cell cycle GO:0046486 glycerolipid metabolic process GO:0046488 phosphatidylinositol metabolic process GO:0046822 regulation of nucleocytoplasmic transport GO:0046824 positive regulation of nucleocytoplasmic transport GO:0046834 lipid phosphorylation GO:0046854 phosphatidylinositol phosphorylation GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling GO:0048514 blood vessel morphogenesis GO:0048732 gland development GO:0048754 branching morphogenesis of an epithelial tube GO:0050730 regulation of peptidyl-tyrosine phosphorylation GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0051048 negative regulation of secretion GO:0051051 negative regulation of transport GO:0051098 regulation of binding GO:0051099 positive regulation of binding GO:0051101 regulation of DNA binding GO:0051169 nuclear transport GO:0051170 nuclear import GO:0051222 positive regulation of protein transport GO:0051783 regulation of nuclear division GO:0051785 positive regulation of nuclear division GO:0051924 regulation of calcium ion transport GO:0051962 positive regulation of nervous system development GO:0060070 canonical Wnt signaling pathway GO:0060562 epithelial tube morphogenesis GO:0060749 mammary gland alveolus development GO:0061097 regulation of protein tyrosine kinase activity GO:0061098 positive regulation of protein tyrosine kinase activity GO:0061138 morphogenesis of a branching epithelium GO:0061351 neural precursor cell proliferation GO:0061377 mammary gland lobule development GO:0070371 ERK1 and ERK2 cascade GO:0070509 calcium ion import GO:0070838 divalent metal ion transport GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0072511 divalent inorganic cation transport GO:0090068 positive regulation of cell cycle process GO:0090279 regulation of calcium ion import GO:0090316 positive regulation of intracellular protein transport GO:0090370 negative regulation of cholesterol efflux GO:0097696 STAT cascade GO:0198738 cell-cell signaling by wnt GO:1900125 regulation of hyaluronan biosynthetic process GO:1900127 positive regulation of hyaluronan biosynthetic process GO:1900180 regulation of protein localization to nucleus GO:1900182 positive regulation of protein localization to nucleus GO:1901184 regulation of ERBB signaling pathway GO:1901185 negative regulation of ERBB signaling pathway GO:1901186 positive regulation of ERBB signaling pathway GO:1902593 single-organism nuclear import GO:1903050 regulation of proteolysis involved in cellular protein catabolic process GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process GO:1903320 regulation of protein modification by small protein conjugation or removal GO:1903322 positive regulation of protein modification by small protein conjugation or removal GO:1903362 regulation of cellular protein catabolic process GO:1903364 positive regulation of cellular protein catabolic process GO:1903510 mucopolysaccharide metabolic process GO:1903533 regulation of protein targeting GO:1903829 positive regulation of cellular protein localization GO:1904589 regulation of protein import GO:1904591 positive regulation of protein import GO:1904951 positive regulation of establishment of protein localization GO:2000008 regulation of protein localization to cell surface GO:2000058 regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:2000060 positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:2000177 regulation of neural precursor cell proliferation GO:2000179 positive regulation of neural precursor cell proliferation GO:2000273 positive regulation of receptor activity
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0005085 guanyl-nucleotide exchange factor activity GO:0005088 Ras guanyl-nucleotide exchange factor activity GO:0005154 epidermal growth factor receptor binding GO:0008047 enzyme activator activity GO:0008083 growth factor activity GO:0017147 Wnt-protein binding GO:0019207 kinase regulator activity GO:0019209 kinase activator activity GO:0019887 protein kinase regulator activity GO:0030295 protein kinase activator activity GO:0030296 protein tyrosine kinase activator activity GO:0030297 transmembrane receptor protein tyrosine kinase activator activity GO:0030545 receptor regulator activity GO:0030546 receptor activator activity GO:0035004 phosphatidylinositol 3-kinase activity GO:0042813 Wnt-activated receptor activity GO:0046934 phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0052813 phosphatidylinositol bisphosphate kinase activity GO:0070851 growth factor receptor binding
Cellular Component	GO:0005765 lysosomal membrane GO:0030141 secretory granule GO:0031091 platelet alpha granule GO:0031093 platelet alpha granule lumen GO:0031983 vesicle lumen GO:0034774 secretory granule lumen GO:0043235 receptor complex GO:0060205 cytoplasmic membrane-bounded vesicle lumen GO:0098852 lytic vacuole membrane GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04010 MAPK signaling pathway hsa04012 ErbB signaling pathway hsa04014 Ras signaling pathway hsa04015 Rap1 signaling pathway hsa04060 Cytokine-cytokine receptor interaction hsa04066 HIF-1 signaling pathway hsa04068 FoxO signaling pathway hsa04144 Endocytosis hsa04151 PI3K-Akt signaling pathway hsa04510 Focal adhesion hsa04540 Gap junction hsa04810 Regulation of actin cytoskeleton
Reactome	R-HSA-170984: ARMS-mediated activation R-HSA-1280218: Adaptive Immune System R-HSA-422475: Axon guidance R-HSA-8856825: Cargo recognition for clathrin-mediated endocytosis R-HSA-8856828: Clathrin-mediated endocytosis R-HSA-2219530: Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-5637810: Constitutive Signaling by EGFRvIII R-HSA-1236382: Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-2172127: DAP12 interactions R-HSA-2424491: DAP12 signaling R-HSA-1266738: Developmental Biology R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-8863795: Downregulation of ERBB2 signaling R-HSA-186763: Downstream signal transduction R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR) R-HSA-182971: EGFR downregulation R-HSA-212718: EGFR interacts with phospholipase C-gamma R-HSA-8847993: ERBB2 Activates PTK6 Signaling R-HSA-6785631: ERBB2 Regulates Cell Motility R-HSA-2871796: FCERI mediated MAPK activation R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-170968: Frs2-mediated activation R-HSA-180292: GAB1 signalosome R-HSA-179812: GRB2 events in EGFR signaling R-HSA-1963640: GRB2 events in ERBB2 signaling R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-109582: Hemostasis R-HSA-2428924: IGF1R signaling cascade R-HSA-112399: IRS-mediated signalling R-HSA-2428928: IRS-related events triggered by IGF1R R-HSA-168256: Immune System R-HSA-5638303: Inhibition of Signaling by Overexpressed EGFR R-HSA-168249: Innate Immune System R-HSA-74751: Insulin receptor signalling cascade R-HSA-912526: Interleukin receptor SHC signaling R-HSA-451927: Interleukin-2 signaling R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-5683057: MAPK family signaling cascades R-HSA-5684996: MAPK1/MAPK3 signaling R-HSA-199991: Membrane Trafficking R-HSA-375165: NCAM signaling for neurite out-growth R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-199418: Negative regulation of the PI3K/AKT network R-HSA-1963642: PI3K events in ERBB2 signaling R-HSA-2219528: PI3K/AKT Signaling in Cancer R-HSA-198203: PI3K/AKT activation R-HSA-6811558: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-1257604: PIP3 activates AKT signaling R-HSA-1251932: PLCG1 events in ERBB2 signaling R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-114608: Platelet degranulation R-HSA-169893: Prolonged ERK activation events R-HSA-5673001: RAF/MAP kinase cascade R-HSA-8853659: RET signaling R-HSA-76005: Response to elevated platelet cytosolic Ca2+ R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization R-HSA-180336: SHC1 events in EGFR signaling R-HSA-1250196: SHC1 events in ERBB2 signaling R-HSA-112412: SOS-mediated signalling R-HSA-162582: Signal Transduction R-HSA-177929: Signaling by EGFR R-HSA-1643713: Signaling by EGFR in Cancer R-HSA-5637812: Signaling by EGFRvIII in Cancer R-HSA-1227986: Signaling by ERBB2 R-HSA-1236394: Signaling by ERBB4 R-HSA-372790: Signaling by GPCR R-HSA-74752: Signaling by Insulin receptor R-HSA-449147: Signaling by Interleukins R-HSA-2586552: Signaling by Leptin R-HSA-5637815: Signaling by Ligand-Responsive EGFR Variants in Cancer R-HSA-5638302: Signaling by Overexpressed Wild-Type EGFR in Cancer R-HSA-186797: Signaling by PDGF R-HSA-8848021: Signaling by PTK6 R-HSA-1433557: Signaling by SCF-KIT R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) R-HSA-194138: Signaling by VEGF R-HSA-983705: Signaling by the B Cell Receptor (BCR) R-HSA-166520: Signalling by NGF R-HSA-187687: Signalling to ERKs R-HSA-167044: Signalling to RAS R-HSA-187706: Signalling to p38 via RIT and RIN R-HSA-4420097: VEGFA-VEGFR2 Pathway R-HSA-5218921: VEGFR2 mediated cell proliferation R-HSA-5653656: Vesicle-mediated transport

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04010 MAPK signaling pathway
hsa04012 ErbB signaling pathway
hsa04014 Ras signaling pathway
hsa04015 Rap1 signaling pathway
hsa04060 Cytokine-cytokine receptor interaction
hsa04066 HIF-1 signaling pathway
hsa04068 FoxO signaling pathway
hsa04144 Endocytosis
hsa04151 PI3K-Akt signaling pathway
hsa04510 Focal adhesion
hsa04540 Gap junction
hsa04810 Regulation of actin cytoskeleton

Reactome

R-HSA-170984: ARMS-mediated activation
R-HSA-1280218: Adaptive Immune System
R-HSA-422475: Axon guidance
R-HSA-8856825: Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828: Clathrin-mediated endocytosis
R-HSA-2219530: Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5637810: Constitutive Signaling by EGFRvIII
R-HSA-1236382: Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-8863795: Downregulation of ERBB2 signaling
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-182971: EGFR downregulation
R-HSA-212718: EGFR interacts with phospholipase C-gamma
R-HSA-8847993: ERBB2 Activates PTK6 Signaling
R-HSA-6785631: ERBB2 Regulates Cell Motility
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-170968: Frs2-mediated activation
R-HSA-180292: GAB1 signalosome
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-1963640: GRB2 events in ERBB2 signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-109582: Hemostasis
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-5638303: Inhibition of Signaling by Overexpressed EGFR
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-5683057: MAPK family signaling cascades
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-199991: Membrane Trafficking
R-HSA-375165: NCAM signaling for neurite out-growth
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-199418: Negative regulation of the PI3K/AKT network
R-HSA-1963642: PI3K events in ERBB2 signaling
R-HSA-2219528: PI3K/AKT Signaling in Cancer
R-HSA-198203: PI3K/AKT activation
R-HSA-6811558: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-1251932: PLCG1 events in ERBB2 signaling
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-114608: Platelet degranulation
R-HSA-169893: Prolonged ERK activation events
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-76005: Response to elevated platelet cytosolic Ca2+
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-1250196: SHC1 events in ERBB2 signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-1643713: Signaling by EGFR in Cancer
R-HSA-5637812: Signaling by EGFRvIII in Cancer
R-HSA-1227986: Signaling by ERBB2
R-HSA-1236394: Signaling by ERBB4
R-HSA-372790: Signaling by GPCR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-5637815: Signaling by Ligand-Responsive EGFR Variants in Cancer
R-HSA-5638302: Signaling by Overexpressed Wild-Type EGFR in Cancer
R-HSA-186797: Signaling by PDGF
R-HSA-8848021: Signaling by PTK6
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
R-HSA-187706: Signalling to p38 via RIT and RIN
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation
R-HSA-5653656: Vesicle-mediated transport

Summary
Symbol	EGF
Name	epidermal growth factor
Aliases	epidermal growth factor (beta-urogastrone); HOMG4; URG; beta-urogastrone; Pro-epidermal growth factor
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between EGF 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 EGF and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27566188	Non-Small Cell Lung Carcinoma	Promote immunity; Essential for immunotherapy	Abnormalities in the epidermal growth factor (EGF) and EGFR pathway promote progression of NSCLC. This concept of pathway targeted immunotherapy (PTI) was validated in vitro by dose-related suppression of EGFR, Akt, and Erk1/2 phosphorylation in cell lines with different mutations.
18349395	Non-Small Cell Lung Carcinoma	Promote immunity; essential for immunotherapy	Phase II randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer. Vaccination with EGF was safe and provoked an increase in anti-EGF antibody titers and a decrease in serum EGF.
27572267	Basal-Like Breast Carcinoma	Inhibit immunity	We also demonstrate that epidermal growth factor (EGF) stabilizes PD-L1 via GSK3β inactivation in basal-like breast cancer. Inhibition of EGF signalling by gefitinib destabilizes PD-L1, enhances antitumour T-cell immunity and therapeutic efficacy of PD-1 blockade in syngeneic mouse models.
18245547	Non-Small Cell Lung Carcinoma	Inhibit immunity	There was a significantly better survival for vaccinated patients that showed the higher capacity to inhibit EGF/EGFR binding and for those who showed an immunodominance by the central region of EGF molecule.
29438695	Triple-Negative Breast Carcinoma	Inhibit immunity	In the study of immune receptor glycosylation, we showed that EGF induces programmed death ligand 1 (PD-L1) and receptor programmed cell death protein 1 (PD-1) interaction, requiring β-1,3-N-acetylglucosaminyl transferase (B3GNT3) expression in triple-negative breast cancer.

Summary
Symbol	EGF
Name	epidermal growth factor
Aliases	epidermal growth factor (beta-urogastrone); HOMG4; URG; beta-urogastrone; Pro-epidermal growth factor
Chromosomal Location	4q25
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 EGF 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	EGF
Name	epidermal growth factor
Aliases	epidermal growth factor (beta-urogastrone); HOMG4; URG; beta-urogastrone; Pro-epidermal growth factor
Chromosomal Location	4q25
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 EGF 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	0.391	0.185
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.31	0.55
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.45	0.303
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.55	0.327
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.344	0.366
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.441	0.779
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.561	0.442
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.102	0.923
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.363	0.217
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.437	0.601
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	-0.428	0.728
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.591	0.0428

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of EGF 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	7.4	6.8	0.6	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	7.4	8.5	-1.1	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	19	5.9	13.1	0.355
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	25	0	25	0.473
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	9.1	6.3	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	5.3	14.8	-9.5	0.224
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	23.1	-18.6	0.134
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	EGF
Name	epidermal growth factor
Aliases	epidermal growth factor (beta-urogastrone); HOMG4; URG; beta-urogastrone; Pro-epidermal growth factor
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of EGF. 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	EGF
Name	epidermal growth factor
Aliases	epidermal growth factor (beta-urogastrone); HOMG4; URG; beta-urogastrone; Pro-epidermal growth factor
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of EGF. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by EGF. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	EGF
Name	epidermal growth factor
Aliases	epidermal growth factor (beta-urogastrone); HOMG4; URG; beta-urogastrone; Pro-epidermal growth factor
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of EGF. 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	EGF
Name	epidermal growth factor
Aliases	epidermal growth factor (beta-urogastrone); HOMG4; URG; beta-urogastrone; Pro-epidermal growth factor
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of EGF expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	EGF
Name	epidermal growth factor
Aliases	epidermal growth factor (beta-urogastrone); HOMG4; URG; beta-urogastrone; Pro-epidermal growth factor
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between EGF and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	EGF
Name	epidermal growth factor
Aliases	epidermal growth factor (beta-urogastrone); HOMG4; URG; beta-urogastrone; Pro-epidermal growth factor
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting EGF collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting EGF.

ID	Name	Drug Type	Targets	#Targets
DB00364	Sucralfate	Small Molecule	EGF, FGA, FGB, FGF2, FGG	5
DB04454	Alpha-Aminobutyric Acid	Small Molecule	EGF, GATM	2
DB08862	Cholecystokinin	Small Molecule	CCKAR, CCKBR, EGF, MAPK3, PRKCB, RAF1	6
DB11973	Tesevatinib	Small Molecule	EGF, EPHB4, ERBB2	3

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