TISIDB

Summary
Symbol	CRP
Name	C-reactive protein, pentraxin-related
Aliases	pentraxin 1; C-reactive protein
Chromosomal Location	1q23.2
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	Secreted.
Domain	PF00354 Pentaxin family
Function	Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphorylcholine. Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0002526 acute inflammatory response GO:0003013 circulatory system process GO:0003018 vascular process in circulatory system GO:0006801 superoxide metabolic process GO:0006909 phagocytosis GO:0006953 acute-phase response GO:0008015 blood circulation GO:0008228 opsonization GO:0009306 protein secretion GO:0010742 macrophage derived foam cell differentiation GO:0010743 regulation of macrophage derived foam cell differentiation GO:0010745 negative regulation of macrophage derived foam cell differentiation GO:0010876 lipid localization GO:0010883 regulation of lipid storage GO:0010888 negative regulation of lipid storage GO:0019915 lipid storage GO:0032637 interleukin-8 production GO:0032677 regulation of interleukin-8 production GO:0032928 regulation of superoxide anion generation GO:0032930 positive regulation of superoxide anion generation GO:0035150 regulation of tube size GO:0042311 vasodilation GO:0042312 regulation of vasodilation GO:0042554 superoxide anion generation GO:0042742 defense response to bacterium GO:0044057 regulation of system process GO:0045908 negative regulation of vasodilation GO:0050663 cytokine secretion GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0050830 defense response to Gram-positive bacterium GO:0050880 regulation of blood vessel size GO:0051235 maintenance of location GO:0072593 reactive oxygen species metabolic process GO:0072606 interleukin-8 secretion GO:0090066 regulation of anatomical structure size GO:0090077 foam cell differentiation GO:0090322 regulation of superoxide metabolic process GO:0098542 defense response to other organism GO:1903522 regulation of blood circulation GO:1903523 negative regulation of blood circulation GO:2000377 regulation of reactive oxygen species metabolic process GO:2000379 positive regulation of reactive oxygen species metabolic process GO:2000482 regulation of interleukin-8 secretion
Molecular Function	GO:0001846 opsonin binding GO:0001848 complement binding GO:0001849 complement component C1q binding GO:0030169 low-density lipoprotein particle binding GO:0033265 choline binding GO:0050750 low-density lipoprotein particle receptor binding GO:0070325 lipoprotein particle receptor binding GO:0070405 ammonium ion binding GO:0071813 lipoprotein particle binding GO:0071814 protein-lipid complex binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-173623: Classical antibody-mediated complement activation R-HSA-166658: Complement cascade R-HSA-166786: Creation of C4 and C2 activators R-HSA-168256: Immune System R-HSA-166663: Initial triggering of complement R-HSA-168249: Innate Immune System

Summary
Symbol	CRP
Name	C-reactive protein, pentraxin-related
Aliases	pentraxin 1; C-reactive protein
Chromosomal Location	1q23.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CRP 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 CRP and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28648699	Uveal Melanoma	Inhibit immunity; Resistant to immunotherapy	Eighty-six patients were treated with PD-1 inhibitors only (n = 54 for pembrolizumab, n = 32 for nivolumab) with a centrally confirmed response rate of 4.7%. Patients with elevated CRP and LDH and a REC <1.5% were at highest risk for disease progression and death (p = 0.001).

Summary
Symbol	CRP
Name	C-reactive protein, pentraxin-related
Aliases	pentraxin 1; C-reactive protein
Chromosomal Location	1q23.2
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 CRP 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	CRP
Name	C-reactive protein, pentraxin-related
Aliases	pentraxin 1; C-reactive protein
Chromosomal Location	1q23.2
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 CRP 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	1.202	0.215
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.082	0.957
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	2.171	0.0908
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.583	0.375
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.546	0.605
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.624	0.597
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.77	0.49
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.573	0.766
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.674	0.712
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.001	0.604
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	2.938	0.225
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.427	0.27

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CRP 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	2.7	1	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	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	5.9	8.4	0.613
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
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	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	10.5	0	10.5	0.135
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	18.2	0	18.2	0.274
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	CRP
Name	C-reactive protein, pentraxin-related
Aliases	pentraxin 1; C-reactive protein
Chromosomal Location	1q23.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CRP. 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	CRP
Name	C-reactive protein, pentraxin-related
Aliases	pentraxin 1; C-reactive protein
Chromosomal Location	1q23.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CRP. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CRP. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CRP
Name	C-reactive protein, pentraxin-related
Aliases	pentraxin 1; C-reactive protein
Chromosomal Location	1q23.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CRP. 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	CRP
Name	C-reactive protein, pentraxin-related
Aliases	pentraxin 1; C-reactive protein
Chromosomal Location	1q23.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CRP expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CRP
Name	C-reactive protein, pentraxin-related
Aliases	pentraxin 1; C-reactive protein
Chromosomal Location	1q23.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CRP and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CRP
Name	C-reactive protein, pentraxin-related
Aliases	pentraxin 1; C-reactive protein
Chromosomal Location	1q23.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CRP collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CRP.

ID	Name	Drug Type	Targets	#Targets
DB03945	N,N,N-Trimethyl-2-(phosphonooxy)ethanaminium	Small Molecule	CRP, ELSPBP1	2
DB05744	CRx-139	Small Molecule	CRP, IL10, IL6, TNF	4

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