CA-125

For the highway, see California State Route 125.

Mucin 16, cell surface associated
Identifiers
Symbols	MUC16; CA125; FLJ14303
External IDs	OMIM: 606154 HomoloGene: 124290 GeneCards: MUC16 Gene
Gene Ontology Molecular function • protein binding Cellular component • extracellular region • extracellular space • plasma membrane • integral to membrane • extrinsic to membrane Biological process • cell adhesion Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	94025	73732
Ensembl	ENSG00000181143	ENSMUSG00000032134
UniProt	B5ME49	Q9D1H1
RefSeq (mRNA)	NM_024690	XM_911929
RefSeq (protein)	NP_078966	XP_917022
Location (UCSC)	Chr 19: 8.96 – 9.09 Mb	Chr 9: 18.3 – 18.32 Mb
PubMed search	[1]	[2]

CA-125 (cancer antigen 125 or carbohydrate antigen 125) also known as mucin 16 or MUC16 is a protein that in humans is encoded by the MUC16 gene.^[1][2] MUC16 is a member of the mucin family glycoproteins.^[3] CA-125 has found application as a tumor marker or biomarker that may be elevated in the blood of some patients with specific types of cancers,^[4] or other benign conditions.

Structure and function

Mucin 16 is a membrane associated mucin that possesses a single transmembrane domain.^[5] MUC16 is a component of the ocular surface (including the cornea and conjunctiva) and the respiratory tract and female reproductive tract epithelia. Mucin 16 plays a role as a lubricating barrier against foreign particles and infectious agents on the surface of epithelial cells.^[6] The expression of mucin 16 has been shown to be altered in dry eye.^[6]

As a biomarker

CA-125 is clinically approved for following the response to treatment and predicting prognosis after treatment. It is especially useful for detecting the recurrence of ovarian cancer. Its potential role for the early detection of ovarian cancer is controversial and has not yet been adopted for widespread screening efforts in asymptomatic women. The key problems in using the CA-125 test as a screening tool are its lack of sensitivity and its inability to detect early stage cancers. An operation would be necessary to confirm that a woman with elevated CA-125 has ovarian cancer, with the associated risk of death from major surgery. In addition, even if cancer was confirmed in such circumstances, it usually would be at an advanced stage where therapy is less effective. The goal of many cancer biologists is to develop a test that would be employed to diagnose ovarian cancer at an early stage, when the effects of therapeutic interventions are optimal.

In April 2011 the UK's National Institute for Health and Clinical Excellence (NICE) recommended that women with symptoms that could be caused by ovarian cancer should be offered a CA-125 blood test^[7]. The aim of this guideline is to help diagnose the disease at an earlier stage, when treatment is more likely to be successful. Women with higher levels of the marker in their blood would then be offered an ultrasound scan to determine whether they need further tests.

Specificity and sensitivity

It is best known as a marker for ovarian cancer,^[8] but it may also be elevated in other cancers, including those originating in the endometrium, fallopian tubes, lungs, breast and gastrointestinal tract.^[4] CA-125 may also be elevated in a number of relatively benign conditions, such as endometriosis,^[9] several diseases of the ovary, and pregnancy.^[10] It also tends to be elevated in the presence of any inflammatory condition in the abdominal area, both cancerous and benign.

Thus, CA-125 is not perfectly specific for cancer nor is it perfectly sensitive since not every patient with cancer will have elevated levels of CA-125 in the blood.^[11] For example, 79% of all ovarian cancers are positive for CA-125, whereas the remainder do not express this antigen at all.^[12]

Ranges in ovarian cancer

While this test is not generally regarded as useful for large scale screening by the medical community, a high value may be an indication that the woman should receive further diagnostic screening or treatment. Normal values range from 0 to 35 (U/mL). Elevated levels in post-menopausal women are usually an indication that further screening is necessary. In pre-menopausal women, the test is less reliable as values are often elevated due to a number of non-cancerous causes, and a value above 35 is not necessarily a cause for concern.

Discovery

ca 125 is a serum marker of CA-125 was initially detected using the monoclonal antibody designated OC125. Dr.s Robert Bast, Robert Knapp and their research team first isolated this monoclonal antibody in 1981.^[13]

References

1. ^ Yin BW, Lloyd KO (July 2001). "Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16". J. Biol. Chem. 276 (29): 27371–5. doi:10.1074/jbc.M103554200. PMID 11369781. 
2. ^ Yin BW, Dnistrian A, Lloyd KO (April 2002). "Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene". Int. J. Cancer 98 (5): 737–40. doi:10.1002/ijc.10250. PMID 11920644. 
3. ^ Duraisamy S, Ramasamy S, Kharbanda S, Kufe D (May 2006). "Distinct evolution of the human carcinoma-associated transmembrane mucins, MUC1, MUC4 AND MUC16". Gene 373: 28–34. doi:10.1016/j.gene.2005.12.021. PMID 16500040. 
4. ^ ^{a b} Bast RC, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB (1998). "CA 125: the past and the future". Int. J. Biol. Markers 13 (4): 179–87. PMID 10228898. 
5. ^ Gipson IK (October 2007). "The ocular surface: the challenge to enable and protect vision: the Friedenwald lecture". Invest. Ophthalmol. Vis. Sci. 48 (10): 4390; 4391–8. doi:10.1167/iovs.07-0770. PMC 2886589. PMID 17898256. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2886589. 
6. ^ ^{a b} Perez BH, Gipson IK (November 2008). "Focus on Molecules: human mucin MUC16". Exp. Eye Res. 87 (5): 400–1. doi:10.1016/j.exer.2007.12.008. PMC 2586928. PMID 18289532. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2586928. 
7. ^ NICE guidance March 2011 press release
8. ^ Osman N, O'Leary N, Mulcahy E, Barrett N, Wallis F, Hickey K, Gupta R (September 2008). "Correlation of serum CA125 with stage, grade and survival of patients with epithelial ovarian cancer at a single centre". Ir Med J 101 (8): 245–7. PMID 18990955. 
9. ^ Bagan P, Berna P, Assouad J, Hupertan V, Le Pimpec Barthes F, Riquet M (January 2008). "Value of cancer antigen 125 for diagnosis of pleural endometriosis in females with recurrent pneumothorax". Eur. Respir. J. 31 (1): 140–2. doi:10.1183/09031936.00094206. PMID 17804443. 
10. ^ Sarandakou A, Protonotariou E, Rizos D (2007). "Tumor markers in biological fluids associated with pregnancy". Crit Rev Clin Lab Sci 44 (2): 151–78. doi:10.1080/10408360601003143. PMID 17364691. 
11. ^ "Screening Asymptomatic Women for Ovarian Cancer: American College of Preventive Medicine Practice Policy". http://www.acpm.org/ovary.htm. Retrieved 2007-09-29. 
12. ^ Rosen DG, Wang L, Atkinson JN, Yu Y, Lu KH, Diamandis EP, Hellstrom I, Mok SC, Liu J, Bast RC (November 2005). "Potential markers that complement expression of CA125 in epithelial ovarian cancer". Gynecol. Oncol. y CA 125 protievolume = 99 99 (2): 267–77. doi:10.1016/j.ygyno.2005.06.040. PMID 16061277. 
13. ^ Bast RC, Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC (November 1981). "Reactivity of a monoclonal antibody with human ovarian carcinoma". J. Clin. Invest. 68 (5): 1331–7. doi:10.1172/JCI110380. PMC 370929. PMID 7028788. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=370929. 

Further reading

• Argüeso P, Guzman-Aranguez A, Mantelli F, et al. (2009). "Association of cell surface mucins with galectin-3 contributes to the ocular surface epithelial barrier.". J. Biol. Chem. 284 (34): 23037–45. doi:10.1074/jbc.M109.033332. PMC 2755710. PMID 19556244. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2755710. 
• Dogru M, Matsumoto Y, Okada N, et al. (2008). "Alterations of the ocular surface epithelial MUC16 and goblet cell MUC5AC in patients with atopic keratoconjunctivitis.". Allergy 63 (10): 1324–34. doi:10.1111/j.1398-9995.2008.01781.x. PMID 18782111. 
• McLemore MR, Aouizerat B (2005). "Introducing the MUC16 gene: implications for prevention and early detection in epithelial ovarian cancer.". Biol Res Nurs 6 (4): 262–7. doi:10.1177/1099800404274445. PMID 15788735. 
• Palmieri RT, Wilson MA, Iversen ES, et al. (2008). "Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women.". Cancer Epidemiol. Biomarkers Prev. 17 (12): 3567–72. doi:10.1158/1055-9965.EPI-08-0548. PMC 2664299. PMID 19064572. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2664299. 
• Sangoi AR, Higgins JP, Rouse RV, et al. (2009). "Immunohistochemical comparison of MUC1, CA125, and Her2Neu in invasive micropapillary carcinoma of the urinary tract and typical invasive urothelial carcinoma with retraction artifact.". Mod. Pathol. 22 (5): 660–7. doi:10.1038/modpathol.2009.16. PMID 19270645. 
• Huhtinen K, Suvitie P, Hiissa J, et al. (2009). "Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts.". Br. J. Cancer 100 (8): 1315–9. doi:10.1038/sj.bjc.6605011. PMC 2676558. PMID 19337252. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2676558. 
• Bekci TT, Senol T, Maden E (2009). "The efficacy of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) levels in determining the malignancy of solitary pulmonary nodules.". J. Int. Med. Res. 37 (2): 438–45. PMID 19383238. 
• Bjerner J, Høgetveit A, Wold Akselberg K, et al. (2008). "Reference intervals for carcinoembryonic antigen (CEA), CA125, MUC1, Alfa-foeto-protein (AFP), neuron-specific enolase (NSE) and CA19.9 from the NORIP study.". Scand. J. Clin. Lab. Invest. 68 (8): 703–13. doi:10.1080/00365510802126836. PMID 18609108. 
• Madendag Y, Col-Madendag I, Kanat-Pektas M, Danisman N (2009). "Predictive power of serum CA-125 and LDH in the outcome of first trimester pregnancies with human chorionic gonadotropin levels below discriminatory zone.". Arch. Gynecol. Obstet. 279 (5): 661–6. doi:10.1007/s00404-008-0798-x. PMID 18797897. 
• Wang ML, Huang Q, Yang TX (2009). "IgE myeloma with elevated level of serum CA125.". Journal of Zhejiang University. Science. B 10 (7): 559–62. doi:10.1631/jzus.B0820399. PMC 2704975. PMID 19585675. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2704975. 
• Camlica H, Duranyildiz D, Tas F, Yasasever V (2008). "Statistical interpretation of CA125 and Bcl-2 in serum of patients with late stage ovarian cancer.". Am. J. Clin. Oncol. 31 (6): 585–8. doi:10.1097/COC.0b013e318174dbd2. PMID 19060592. 
• Caffery B, Joyce E, Heynen ML, et al. (2008). "MUC16 expression in Sjogren's syndrome, KCS, and control subjects.". Mol. Vis. 14: 2547–55. PMC 2613075. PMID 19122828. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2613075. 
• Prat A, Parera M, Adamo B, et al. (2009). "Risk of recurrence during follow-up for optimally treated advanced epithelial ovarian cancer (EOC) with a low-level increase of serum CA-125 levels.". Ann. Oncol. 20 (2): 294–7. doi:10.1093/annonc/mdn601. PMID 18820245. 
• de Larrea CF, Cibeira MT, Vallansot R, et al. (2008). "Increased serum tumor markers (CA125 and CA15.3) in primary plasma cell leukemia: a case report and review of the literature.". Clinical lymphoma & myeloma 8 (5): 312–4. doi:10.3816/CLM.2008.n.045. PMID 18854288. 
• Cebesoy FB, Balat O, Dikensoy E, et al. (2009). "CA-125 and CRP are elevated in preeclampsia.". Hypertens Pregnancy 28 (2): 201–11. doi:10.1080/10641950802601187. PMID 19437230. 
• Yu B, Xu PZ, Wang QW, et al. (2009). "Clinical value of tumour specific growth factor (TSGF) and carbohydrate antigen-125 (CA-125) in carcinoma of the endometrium.". J. Int. Med. Res. 37 (3): 878–83. PMID 19589273. 
• Kaneko O, Gong L, Zhang J, et al. (2009). "A binding domain on mesothelin for CA125/MUC16.". J. Biol. Chem. 284 (6): 3739–49. doi:10.1074/jbc.M806776200. PMC 2635045. PMID 19075018. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2635045. 
• Kouba EJ, Lentz A, Wallen EM, Pruthi RS (2009). "Clinical use of serum CA-125 levels in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder.". Urol. Oncol. 27 (5): 486–90. doi:10.1016/j.urolonc.2008.03.019. PMID 18555706. 
• Samuels TL, Handler E, Syring ML, et al. (2008). "Mucin gene expression in human laryngeal epithelia: effect of laryngopharyngeal reflux.". Ann. Otol. Rhinol. Laryngol. 117 (9): 688–95. PMID 18834073. 
• De Gennaro L, Brunetti ND, Bungaro R, et al. (2009). "Carbohydrate antigen-125: additional accuracy in identifying patients at risk of acute heart failure in acute coronary syndrome.". Coron. Artery Dis. 20 (4): 274–80. doi:10.1097/MCA.0b013e3283229d82. PMID 19440066. 

External links

• CA-125 blood test urban legend at snopes.com
• MeSH CA-125+Antigen