Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLL9WWO)

DOT Name	Carcinoembryonic antigen-related cell adhesion molecule 8 (CEACAM8)
Synonyms	CD67 antigen; Carcinoembryonic antigen CGM6; Non-specific cross-reacting antigen NCA-95; CD antigen CD66b
Gene Name	CEACAM8
Related Disease	Neoplasm ( ) Ovarian neoplasm ( ) Rheumatoid arthritis ( ) Abscess ( ) Breast cancer ( ) Breast carcinoma ( ) Childhood acute lymphoblastic leukemia ( ) Colon cancer ( ) Colorectal carcinoma ( ) Crohn disease ( ) Cutaneous leishmaniasis ( ) Cystic fibrosis ( ) Dengue ( ) Liver cirrhosis ( ) Myelodysplastic syndrome ( ) Oral mucosa leukoplakia ( ) Disseminated intravascular coagulation ( ) Acute lymphocytic leukaemia ( ) Aplastic anemia ( ) Eosinophilic esophagitis ( ) Hepatocellular carcinoma ( ) Obesity ( ) Paroxysmal nocturnal haemoglobinuria ( )
UniProt ID	CEAM8_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2DKS; 4WTZ; 4Y88; 4YIQ
Pfam ID	PF13895 ; PF13927 ; PF07686
Sequence	MGPISAPSCRWRIPWQGLLLTASLFTFWNPPTTAQLTIEAVPSNAAEGKEVLLLVHNLPQ DPRGYNWYKGETVDANRRIIGYVISNQQITPGPAYSNRETIYPNASLLMRNVTRNDTGSY TLQVIKLNLMSEEVTGQFSVHPETPKPSISSNNSNPVEDKDAVAFTCEPETQNTTYLWWV NGQSLPVSPRLQLSNGNRTLTLLSVTRNDVGPYECEIQNPASANFSDPVTLNVLYGPDAP TISPSDTYYHAGVNLNLSCHAASNPPSQYSWSVNGTFQQYTQKLFIPNITTKNSGSYACH TTNSATGRNRTTVRMITVSDALVQGSSPGLSARATVSIMIGVLARVALI
Function	Cell surface glycoprotein that plays a role in cell adhesion in a calcium-independent manner. Mediates heterophilic cell adhesion with other carcinoembryonic antigen-related cell adhesion molecules, such as CEACAM6. Heterophilic interaction with CEACAM8 occurs in activated neutrophils.
Tissue Specificity	Expressed in leukocytes of chronic myeloid Leukemia patients and bone marrow.
Reactome Pathway	Cell surface interactions at the vascular wall (R-HSA-202733 ) Neutrophil degranulation (R-HSA-6798695 ) Fibronectin matrix formation (R-HSA-1566977 )

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Altered Expression	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[3]
Abscess	DISAP982	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[6]
Colon cancer	DISVC52G	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Crohn disease	DIS2C5Q8	Strong	Altered Expression	[9]
Cutaneous leishmaniasis	DISRK7TS	Strong	Altered Expression	[10]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[11]
Dengue	DISKH221	Strong	Altered Expression	[12]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[13]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[14]
Oral mucosa leukoplakia	DISJTL5X	Strong	Biomarker	[4]
Disseminated intravascular coagulation	DISCAVOZ	moderate	Biomarker	[15]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Altered Expression	[6]
Aplastic anemia	DISJRSC0	Limited	Biomarker	[16]
Eosinophilic esophagitis	DISR8WSB	Limited	Altered Expression	[17]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[18]
Obesity	DIS47Y1K	Limited	Biomarker	[19]
Paroxysmal nocturnal haemoglobinuria	DISBHMYH	Limited	Biomarker	[16]
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⏷ Show the Full List of 23 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Carcinoembryonic antigen-related cell adhesion molecule 8 (CEACAM8).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Carcinoembryonic antigen-related cell adhesion molecule 8 (CEACAM8).	[22]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 8 (CEACAM8).	[21]
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References

1	High CD3(+) lymphocytes, low CD66b(+) neutrophils, and scarce tumor budding in the invasive front of lip squamous cell carcinomas.Arch Oral Biol. 2019 Aug;104:46-51. doi: 10.1016/j.archoralbio.2019.05.027. Epub 2019 May 27.
2	A polymerase-chain-reaction assay for the specific identification of transcripts encoded by individual carcinoembryonic antigen (CEA)-gene-family members.Int J Cancer. 1993 Sep 9;55(2):311-9. doi: 10.1002/ijc.2910550223.
3	Extracellular Chromatin Triggers Release of Soluble CEACAM8 Upon Activation of Neutrophils.Front Immunol. 2019 Jun 14;10:1346. doi: 10.3389/fimmu.2019.01346. eCollection 2019.
4	Immunohistochemical analysis of neutrophils, interleukin-17, matrix metalloproteinase-9, and neoformed vessels in oral squamous cell carcinoma.J Oral Pathol Med. 2018 Oct;47(9):856-863. doi: 10.1111/jop.12762. Epub 2018 Jul 18.
5	Co-expression of carcinoembryonic antigen-related cell adhesion molecule 6 and 8 inhibits proliferation and invasiveness of breast carcinoma cells.Clin Exp Metastasis. 2019 Oct;36(5):423-432. doi: 10.1007/s10585-019-09981-2. Epub 2019 Jun 20.
6	High expression of CEACAM6 and CEACAM8 mRNA in acute lymphoblastic leukemias.Ann Hematol. 2008 Mar;87(3):205-11. doi: 10.1007/s00277-007-0388-1. Epub 2007 Oct 2.
7	Neutrophil infiltration is a favorable prognostic factor in early stages of colon cancer.Hum Pathol. 2017 Oct;68:193-202. doi: 10.1016/j.humpath.2017.08.028. Epub 2017 Sep 4.
8	A Risk Signature With Inflammatory and T Immune Cells Infiltration in Colorectal Cancer Predicting Distant Metastases and Efficiency of Chemotherapy.Front Oncol. 2019 Aug 13;9:704. doi: 10.3389/fonc.2019.00704. eCollection 2019.
9	Recruitment of activated neutrophils correlates with disease severity in adult Crohn's disease.Clin Exp Immunol. 2019 Feb;195(2):251-264. doi: 10.1111/cei.13226. Epub 2018 Nov 28.
10	Leishmania braziliensis isolated from disseminated leishmaniasis patients downmodulate neutrophil function.Parasite Immunol. 2019 May;41(5):e12620. doi: 10.1111/pim.12620.
11	G-CSF and GM-CSF Modify Neutrophil Functions at Concentrations found in Cystic Fibrosis.Sci Rep. 2019 Sep 10;9(1):12937. doi: 10.1038/s41598-019-49419-z.
12	Neutrophil Activation and Early Features of NET Formation Are Associated With Dengue Virus Infection in Human.Front Immunol. 2019 Jan 11;9:3007. doi: 10.3389/fimmu.2018.03007. eCollection 2018.
13	Dysfunctional neutrophil effector organelle mobilization and microbicidal protein release in alcohol-related cirrhosis.Am J Physiol Gastrointest Liver Physiol. 2017 Sep 1;313(3):G203-G211. doi: 10.1152/ajpgi.00112.2016. Epub 2017 Jun 22.
14	Reduced expression of flavocytochrome b558, a component of the NADPH oxidase complex, in neutrophils from patients with myelodysplasia.Exp Hematol. 2003 Sep;31(9):752-9. doi: 10.1016/s0301-472x(03)00188-7.
15	Evidence of Netosis in Septic Shock-Induced Disseminated Intravascular Coagulation.Shock. 2017 Mar;47(3):313-317. doi: 10.1097/SHK.0000000000000719.
16	Value of CD16/CD66b/CD45 in comparison to CD55/CD59/CD45 in diagnosis of paroxysmal nocturnal haemoglobinuria: An Indian experience.Indian J Med Res. 2017 Sep;146(3):362-368. doi: 10.4103/ijmr.IJMR_195_14.
17	Immunophenotyping of peripheral eosinophils demonstrates activation in eosinophilic esophagitis.J Pediatr Gastroenterol Nutr. 2011 Jul;53(1):40-7. doi: 10.1097/MPG.0b013e318212647a.
18	Cancer-associated fibroblasts induce PDL1+ neutrophils through the IL6-STAT3 pathway that foster immune suppression in hepatocellular carcinoma.Cell Death Dis. 2018 Apr 1;9(4):422. doi: 10.1038/s41419-018-0458-4.
19	Plasma protein biomarkers and their association with mutually exclusive cardiovascular phenotypes: the FIBRO-TARGETS case-control analyses.Clin Res Cardiol. 2020 Jan;109(1):22-33. doi: 10.1007/s00392-019-01480-4. Epub 2019 May 6.
20	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
21	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
22	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.