CA-125

For the highway, see California State Route 125.
Mucin 16, cell surface associated

Identifiers
Symbols MUC16 ; CA125
External IDs OMIM: 606154 HomoloGene: 133291 GeneCards: MUC16 Gene
Orthologs
Species Human Mouse
Entrez 94025 73732
Ensembl ENSG00000181143 ENSMUSG00000032134
UniProt Q8WXI7 Q9D1H1
RefSeq (mRNA) NM_024690 n/a
RefSeq (protein) NP_078966 n/a
Location (UCSC) Chr 19:
8.85 – 8.98 Mb		 Chr 9:
18.3 – 18.32 Mb
PubMed search

CA-125 (cancer antigen 125, carcinoma 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 conditions that are benign.

Structure

Mucin 16 is a membrane associated mucin that possesses a single transmembrane domain.[5] A unique property of MUC16 is its large size. MUC16 is more than twice as long as MUC1 and MUC4 and contains about 22,000 amino acids, making it the largest membrane-associated mucin.[6]

MUC16 is composed of three different domains:[7]

The N-terminal and tandem repeat domains are both entirely extracellular and highly O-glycosylated. All mucins contain a tandem repeat domain that has repeating amino acid sequences high in serine, threonine and proline.[8] The C-terminal domain contains multiple extracellular SEA (sea urchin sperm protein, enterokinase, and agrin) modules,[9] a transmembrane domain, and a cytoplasmic tail.[7] The extracellular region of MUC16 can be released from the cell surface by undergoing proteolytic cleavage.[10] MUC16 is thought to be cleaved at a site in the SEA modules.[11]

Function

MUC16 is a component of the ocular surface (including the cornea and conjunctiva), the respiratory tract and the female reproductive tract epithelia. Since MUC16 is highly glycosylated it creates a hydrophilic environment that acts as a lubricating barrier against foreign particles and infectious agents on the apical membrane of epithelial cells.[12] Also, the cytoplasmic tail of MUC16 has been shown to interact with cytoskeleton by binding members of the ERM protein family.[13] The expression of mucin 16 has been shown to be altered in dry eye, cystic fibrosis, and several types of cancers.[14]

As a biomarker

CA-125 is the most frequently used biomarker for ovarian cancer detection.[15] Medical societies including American Congress of Obstetricians and Gynecologists recommend against women with average risk of ovarian cancer having routine CA-125 screening or other screening for this cancer.[16] Reasons for this include evidence that ambiguous test results are more likely to lead to further invasive, harmful, and unnecessary health care than they are likely to detect ovarian cancer in women who are at average risk of developing it.[16]

Around 90% of women with advanced ovarian cancer have elevated levels of CA-125 in their blood serum, making CA-125 a useful tool for detecting ovarian cancer after the onset of symptoms.[17] Monitoring CA-125 blood serum levels is also useful for determining how ovarian cancer is responding to treatment (with the duration of disease-free survival correlating with the rate of fall of CA-125)[18] and for predicting a patient’s prognosis after treatment.[19] This is because the persistence of high levels of CA-125 during therapy is associated with poor survival rates in patients.[19] Also, an increase in CA-125 levels within individuals in a remission is a strong predictor of the recurrence of ovarian cancer.[20] Indeed, a rising CA-125 level may precede clinical evidence of disease relapse by an interval of 3 to 6 months.

Prognosis relates to both the initial and post-treatment CA-125 values. A preoperative value >65 U/mL suggests a poor prognosis. Persistent elevations following chemotherapy indicate a poor prognosis. The half-life of CA-125 after chemotherapy correlates with prognosis (patients with CA-125 half-life <20 days show improved survival). Time-to-normalization (rate of fall of CA-125) affects prognosis with more rapid normalization within 3 cycles of chemotherapy correlating with improved survival.[21]

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.[22] 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.

In one case, elevated serum levels of CA-125 were observed in a male patient with IgE myeloma, however more cases are needed to determine the clinical significance of CA-125 in myeloma.[23]

Early detection of ovarian cancer

The potential role of CA-125 for the early detection of ovarian cancer is controversial and has not yet been adopted for widespread screening efforts in asymptomatic women.[24][25] The major issues with using the CA-125 biomarker are its lack of sensitivity, particularly for detecting early stages of ovarian cancer, and its lack of specificity, especially in premenopausal women.[26] These limitations mean that CA-125 testing often gives false positives for ovarian cancer and puts patients through unnecessary further screening (sometimes including surgery) and anxiety.[20] Also, these limitations mean that many women with early stage ovarian cancer will receive a false negative from CA-125 testing and not get further treatment for their condition.[27]

Specificity and sensitivity

CA-125 has limited specificity for ovarian cancer because elevated CA-125 levels can be found in individuals without ovarian cancer. For example, while CA-125 is best known as a marker for ovarian cancer,[28] it may also be elevated in other cancers, including endometrial cancer, fallopian tube cancer, lung cancer, breast cancer and gastrointestinal cancer.[4] CA-125 may also be elevated in a number of relatively benign conditions, such as endometriosis,[29] several diseases of the ovary, menstruation[26] and pregnancy.[30] It also tends to be elevated in the presence of any inflammatory condition in the abdominal area, both cancerous and benign,[31] as well as in cirrhosis and diabetes mellitus.[32] Thus, CA-125 testing is not perfectly specific for ovarian cancer and often results in false positives.[26]

The specificity of CA-125 is particularly low in premenopausal women because many benign conditions that cause fluctuations in CA-125 levels, such as menstruation, pregnancy, and pelvic inflammatory disease, are seen in this population.[25]

CA-125 testing is also not perfectly sensitive for detecting ovarian cancer because not every patient with cancer will have elevated levels of CA-125 in their blood.[33] For example, 79% of all ovarian cancers are positive for CA-125, whereas the remainder do not express this antigen at all.[34] Also, only about 50% of patients with early stage ovarian cancer have elevated CA-125 levels, meaning that CA-125 has particularly poor sensitivity for ovarian cancer before the onset of symptoms.[26][35] Poor sensitivity means that the use of CA-125 to detect ovarian cancer (especially in early stages of disease) can frequently lead to false negatives. Patients that receive false negatives are unlikely to seek further treatment for their disease.

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).[26] 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.[25]

In a patient who is clinically selected for testing due to the presence of an adnexal/pelvic mass, CA-125 has great utility to differentiate benign from malignant processes. In a post-menopausal woman with a palpable adnexal mass and CA-125 level greater than 65 U/mL, the positive predictive value is >95% for ovarian malignancy. In patients who are not as carefully selected clinically, the utility of this test decreases, thus highlighting the need for careful clinical scrutiny.

Role in cancer

Tumor metastasis initiated by interactions between MUC16 and mesothelin.

MUC16 (CA-125) has been shown to play a role in advancing tumorigenesis and tumor proliferation by several different mechanisms.

Immune system evasion

One way that MUC16 helps the growth of tumors is by suppressing the response of natural killer cells, thereby protecting cancer cells from the immune response.[36] Further evidence that MUC16 can protect tumor cells from the immune system is the discovery that the heavily glycosylated tandem repeat domain of MUC16 can bind to galectin-1 (an immunosuppressive protein).[37]

Metastatic invasion

MUC16 is also thought to participate in cell-to-cell interactions that enable the metastasis of tumor cells. This is supported by evidence showing that MUC16 binds selectively to mesothelin, a glycoprotein normally expressed by the mesothelial cells of the peritoneum (the lining of the abdominal cavity).[38] MUC16 and mesothelin interactions are thought to provide the first step in tumor cell invasion of the peritoneum.[39]

Mesothelin has also been found to be expressed in several types of cancers including mesothelioma, ovarian cancer and squamous cell carcinoma.[40] Since mesothelin is also expressed by tumor cells, MUC16 and mesothelial interactions may aid in the gathering of other tumor cells to the location of a metastasis, thus increasing the size of the metastasis.[39]

Induced motility

Evidence suggests that expression of the cytoplasmic tail of MUC16 enables tumor cells to grow, promotes cell motility and may facilitate invasion. This appears to be due to the ability of the C-terminal domain of MUC16 to facilitate signaling that leads to a decrease in the expression of E-cadherin and increase the expression of N-cadherin and vimentin, which are expression patterns consistent with epithelial-mesenchymal transition.[41]

Chemotherapy resistance

MUC16 may also play a role in reducing the sensitivity of cancer cells to drug therapy. For example, overexpression of MUC16 has been shown to protect cells from the effects of genotoxic drugs, such as cisplatin.[42]

Discovery

CA-125 was initially detected using the murine monoclonal antibody designated OC125. Robert Bast, Robert Knapp and their research team first isolated this monoclonal antibody in 1981.[43] The protein was named “cancer antigen 125” because OC125 was the 125th antibody produced against the ovarian cancer cell line that was being studied.[44]

References

  1. ↑ Yin BW, Lloyd KO (Jul 2001). "Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16". The Journal of Biological Chemistry 276 (29): 27371–5. doi:10.1074/jbc.M103554200. PMID 11369781.
  2. ↑ Yin BW, Dnistrian A, Lloyd KO (Apr 2002). "Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene". International Journal of Cancer. Journal International Du 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. 1 2 Bast RC, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB (1998). "CA 125: the past and the future". The International Journal of Biological Markers 13 (4): 179–87. PMID 10228898.
  5. ↑ Gipson IK (Oct 2007). "The ocular surface: the challenge to enable and protect vision: the Friedenwald lecture". Investigative Ophthalmology & Visual Science 48 (10): 4390; 4391–8. doi:10.1167/iovs.07-0770. PMC 2886589. PMID 17898256.
  6. ↑ Gniewek P, Kolinski A (Jan 2012). "Coarse-grained modeling of mucus barrier properties". Biophysical Journal 102 (2): 195–200. doi:10.1016/j.bpj.2011.11.4010. PMC 3260744. PMID 22339855.
  7. 1 2 O'Brien TJ, Beard JB, Underwood LJ, Dennis RA, Santin AD, York L (Nov–Dec 2001). "The CA 125 gene: an extracellular superstructure dominated by repeat sequences". Tumour Biology 22 (6): 348–66. doi:10.1159/000050638. PMID 11786729.
  8. ↑ Hollingsworth MA, Swanson BJ (Jan 2004). "Mucins in cancer: protection and control of the cell surface". Nature Reviews. Cancer 4 (1): 45–60. doi:10.1038/nrc1251. PMID 14681689.
  9. ↑ Kufe DW (Dec 2009). "Mucins in cancer: function, prognosis and therapy". Nature Reviews. Cancer 9 (12): 874–85. doi:10.1038/nrc2761. PMC 2951677. PMID 19935676.
  10. ↑ Goodell CA, Belisle JA, Gubbels JA, Migneault M, Rancourt C, Connor J, Kunnimalaiyaan M, Kravitz R, Tucker W, Zwick M, Patankar MS (2009). "Characterization of the tumor marker muc16 (ca125) expressed by murine ovarian tumor cell lines and identification of a panel of cross-reactive monoclonal antibodies". Journal of Ovarian Research 2 (1): 8. doi:10.1186/1757-2215-2-8. PMC 2708168. PMID 19538730.
  11. ↑ Palmai-Pallag T, Khodabukus N, Kinarsky L, Leir SH, Sherman S, Hollingsworth MA, Harris A (Jun 2005). "The role of the SEA (sea urchin sperm protein, enterokinase and agrin) module in cleavage of membrane-tethered mucins". The FEBS Journal 272 (11): 2901–11. doi:10.1111/j.1742-4658.2005.04711.x. PMID 15943821.
  12. ↑ Perez BH, Gipson IK (Nov 2008). "Focus on Molecules: human mucin MUC16". Experimental Eye Research 87 (5): 400–1. doi:10.1016/j.exer.2007.12.008. PMC 2586928. PMID 18289532.
  13. ↑ Blalock TD, Spurr-Michaud SJ, Tisdale AS, Heimer SR, Gilmore MS, Ramesh V, Gipson IK (Oct 2007). "Functions of MUC16 in corneal epithelial cells". Investigative Ophthalmology & Visual Science 48 (10): 4509–18. doi:10.1167/iovs.07-0430. PMID 17898272.
  14. ↑ Bafna S, Kaur S, Batra SK (May 2010). "Membrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cells". Oncogene 29 (20): 2893–904. doi:10.1038/onc.2010.87. PMC 2879972. PMID 20348949.
  15. ↑ Suh KS, Park SW, Castro A, Patel H, Blake P, Liang M, Goy A (Nov 2010). "Ovarian cancer biomarkers for molecular biosensors and translational medicine". Expert Review of Molecular Diagnostics 10 (8): 1069–83. doi:10.1586/erm.10.87. PMID 21080822.
  16. 1 2 American Congress of Obstetricians and Gynecologists, "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation (American Congress of Obstetricians and Gynecologists), retrieved August 1, 2013, which cites
  17. ↑ Gupta D, Lis CG (2010). "Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature". Nutrition Journal 9: 69. doi:10.1186/1475-2891-9-69. PMC 3019132. PMID 21176210.
  18. ↑ Bast RC, Klug TL, St John E, Jenison E, Niloff JM, Lazarus H, Berkowitz RS, Leavitt T, Griffiths CT, Parker L, Zurawski VR, Knapp RC (Oct 1983). "A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer". The New England Journal of Medicine 309 (15): 883–7. doi:10.1056/NEJM198310133091503. PMID 6310399.
  19. 1 2 Göcze P, Vahrson H (Apr 1993). "[Ovarian carcinoma antigen (CA 125) and ovarian cancer (clinical follow-up and prognostic studies)]". Orvosi Hetilap (in Hungarian) 134 (17): 915–8. PMID 8479736.
  20. 1 2 Santillan A, Garg R, Zahurak ML, Gardner GJ, Giuntoli RL, Armstrong DK, Bristow RE (Dec 2005). "Risk of epithelial ovarian cancer recurrence in patients with rising serum CA-125 levels within the normal range". Journal of Clinical Oncology 23 (36): 9338–43. doi:10.1200/JCO.2005.02.2582. PMID 16361633.
  21. ↑ Mais DD, Leonard GR (2009). Quick Compendium Companion for Clinical Pathology (2nd ed.). Chicago: American Society for Clinical Pathology. p. 352. ISBN 0-89189-579-5.
  22. ↑ "Women should be offered a blood test for ovarian cancer". NICE guidance. United Kingdom National Institute for Health and Clinical Excellence. 2011-04-27. Retrieved 2012-04-14.
  23. ↑ Wang ML, Huang Q, Yang TX (Jul 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.
  24. ↑ Baron JA (May 2012). "Screening for cancer with molecular markers: progress comes with potential problems". Nature Reviews. Cancer 12 (5): 368–71. doi:10.1038/nrc3260. PMID 22495319.
  25. 1 2 3 Fritsche HA, Bast RC (Jul 1998). "CA 125 in ovarian cancer: advances and controversy". Clinical Chemistry 44 (7): 1379–80. PMID 9665412.
  26. 1 2 3 4 5 Nossov V, Amneus M, Su F, Lang J, Janco JM, Reddy ST, Farias-Eisner R (Sep 2008). "The early detection of ovarian cancer: from traditional methods to proteomics. Can we really do better than serum CA-125?". American Journal of Obstetrics and Gynecology 199 (3): 215–23. doi:10.1016/j.ajog.2008.04.009. PMID 18468571.
  27. ↑ Moss EL, Hollingworth J, Reynolds TM (Mar 2005). "The role of CA125 in clinical practice". Journal of Clinical Pathology 58 (3): 308–12. doi:10.1136/jcp.2004.018077. PMC 1770590. PMID 15735166.
  28. ↑ Osman N, O'Leary N, Mulcahy E, Barrett N, Wallis F, Hickey K, Gupta R (Sep 2008). "Correlation of serum CA125 with stage, grade and survival of patients with epithelial ovarian cancer at a single centre". Irish Medical Journal 101 (8): 245–7. PMID 18990955.
  29. ↑ Bagan P, Berna P, Assouad J, Hupertan V, Le Pimpec Barthes F, Riquet M (Jan 2008). "Value of cancer antigen 125 for diagnosis of pleural endometriosis in females with recurrent pneumothorax". The European Respiratory Journal 31 (1): 140–2. doi:10.1183/09031936.00094206. PMID 17804443.
  30. ↑ Sarandakou A, Protonotariou E, Rizos D (2007). "Tumor markers in biological fluids associated with pregnancy". Critical Reviews in Clinical Laboratory Sciences 44 (2): 151–78. doi:10.1080/10408360601003143. PMID 17364691.
  31. ↑ Asher V, Hammond R, Duncan TJ (2010). "Pelvic mass associated with raised CA 125 for benign condition: a case report". World Journal of Surgical Oncology 8: 28. doi:10.1186/1477-7819-8-28. PMC 2861664. PMID 20398372.
  32. ↑ Faulkner D, Meldrum C (2012). "Tumour markers". Australian Prescriber 35 (4): 125–8.
  33. ↑ Ferrini R (1997). "Screening asymptomatic women for ovarian cancer: American College of Preventive Medicine practice policy" (PDF). American Journal of Preventive Medicine 13 (6): 444–6. PMID 9415790.
  34. ↑ Rosen DG, Wang L, Atkinson JN, Yu Y, Lu KH, Diamandis EP, Hellstrom I, Mok SC, Liu J, Bast RC (Nov 2005). "Potential markers that complement expression of CA125 in epithelial ovarian cancer". Gynecologic Oncology 99 (2): 267–77. doi:10.1016/j.ygyno.2005.06.040. PMID 16061277.
  35. ↑ Sasaroli D, Coukos G, Scholler N (Jun 2009). "Beyond CA125: the coming of age of ovarian cancer biomarkers. Are we there yet?". Biomarkers in Medicine 3 (3): 275–288. doi:10.2217/bmm.09.21. PMC 2726755. PMID 19684876.
  36. ↑ Patankar MS, Jing Y, Morrison JC, Belisle JA, Lattanzio FA, Deng Y, Wong NK, Morris HR, Dell A, Clark GF (Dec 2005). "Potent suppression of natural killer cell response mediated by the ovarian tumor marker CA125". Gynecologic Oncology 99 (3): 704–13. doi:10.1016/j.ygyno.2005.07.030. PMID 16126266.
  37. ↑ Seelenmeyer C, Wegehingel S, Lechner J, Nickel W (Apr 2003). "The cancer antigen CA125 represents a novel counter receptor for galectin-1". Journal of Cell Science 116 (Pt 7): 1305–18. doi:10.1242/jcs.00312. PMID 12615972.
  38. ↑ Rump A, Morikawa Y, Tanaka M, Minami S, Umesaki N, Takeuchi M, Miyajima A (Mar 2004). "Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion". The Journal of Biological Chemistry 279 (10): 9190–8. doi:10.1074/jbc.M312372200. PMID 14676194.
  39. 1 2 Gubbels JA, Belisle J, Onda M, Rancourt C, Migneault M, Ho M, Bera TK, Connor J, Sathyanarayana BK, Lee B, Pastan I, Patankar MS (2006). "Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors". Molecular Cancer 5 (1): 50. doi:10.1186/1476-4598-5-50. PMC 1635730. PMID 17067392.
  40. ↑ Chang K, Pastan I (Jan 1996). "Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers". Proceedings of the National Academy of Sciences of the United States of America 93 (1): 136–40. doi:10.1073/pnas.93.1.136. PMC 40193. PMID 8552591.
  41. ↑ Thériault C, Pinard M, Comamala M, Migneault M, Beaudin J, Matte I, Boivin M, Piché A, Rancourt C (Jun 2011). "MUC16 (CA125) regulates epithelial ovarian cancer cell growth, tumorigenesis and metastasis". Gynecologic Oncology 121 (3): 434–43. doi:10.1016/j.ygyno.2011.02.020. PMID 21421261.
  42. ↑ Boivin M, Lane D, Piché A, Rancourt C (Dec 2009). "CA125 (MUC16) tumor antigen selectively modulates the sensitivity of ovarian cancer cells to genotoxic drug-induced apoptosis". Gynecologic Oncology 115 (3): 407–13. doi:10.1016/j.ygyno.2009.08.007. PMID 19747716.
  43. ↑ Bast RC, Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC (Nov 1981). "Reactivity of a monoclonal antibody with human ovarian carcinoma". The Journal of Clinical Investigation 68 (5): 1331–7. doi:10.1172/JCI110380. PMC 370929. PMID 7028788.
  44. ↑ Schmidt C (Sep 2011). "CA-125: a biomarker put to the test". Journal of the National Cancer Institute 103 (17): 1290–1. doi:10.1093/jnci/djr344. PMID 21852262.

Further reading

  • Argüeso P, Guzman-Aranguez A, Mantelli F, Cao Z, Ricciuto J, Panjwani N (Aug 2009). "Association of cell surface mucins with galectin-3 contributes to the ocular surface epithelial barrier". The Journal of Biological Chemistry 284 (34): 23037–45. doi:10.1074/jbc.M109.033332. PMC 2755710. PMID 19556244. 
  • Dogru M, Matsumoto Y, Okada N, Igarashi A, Fukagawa K, Shimazaki J, Tsubota K, Fujishima H (Oct 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 (Apr 2005). "Introducing the MUC16 gene: implications for prevention and early detection in epithelial ovarian cancer". Biological Research for Nursing 6 (4): 262–7. doi:10.1177/1099800404274445. PMID 15788735. 
  • Palmieri RT, Wilson MA, Iversen ES, Clyde MA, Calingaert B, Moorman PG, Poole C, Anderson AR, Anderson S, Anton-Culver H, Beesley J, Hogdall E, Brewster W, Carney ME, Chen X, Chenevix-Trench G, Chang-Claude J, Cunningham JM, Dicioccio RA, Doherty JA, Easton DF, Edlund CK, Gayther SA, Gentry-Maharaj A, Goode EL, Goodman MT, Kjaer SK, Hogdall CK, Hopkins MP, Jenison EL, Blaakaer J, Lurie G, McGuire V, Menon U, Moysich KB, Ness RB, Pearce CL, Pharoah PD, Pike MC, Ramus SJ, Rossing MA, Song H, Terada KY, Vandenberg D, Vierkant RA, Wang-Gohrke S, Webb PM, Whittemore AS, Wu AH, Ziogas A, Berchuck A, Schildkraut JM (Dec 2008). "Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women". Cancer Epidemiology, Biomarkers & Prevention 17 (12): 3567–72. doi:10.1158/1055-9965.EPI-08-0548. PMC 2664299. PMID 19064572. 
  • Sangoi AR, Higgins JP, Rouse RV, Schneider AG, McKenney JK (May 2009). "Immunohistochemical comparison of MUC1, CA125, and Her2Neu in invasive micropapillary carcinoma of the urinary tract and typical invasive urothelial carcinoma with retraction artifact". Modern Pathology 22 (5): 660–7. doi:10.1038/modpathol.2009.16. PMID 19270645. 
  • Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H, Setälä M, Härkki P, Jalkanen J, Fraser J, Mäkinen J, Auranen A, Poutanen M, Perheentupa A (Apr 2009). "Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts". British Journal of Cancer 100 (8): 1315–9. doi:10.1038/sj.bjc.6605011. PMC 2676558. PMID 19337252. 
  • 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". The Journal of International Medical Research 37 (2): 438–45. doi:10.1177/147323000903700219. PMID 19383238. 
  • Bjerner J, Høgetveit A, Wold Akselberg K, Vangsnes K, Paus E, Bjøro T, Børmer OP, Nustad K (2008). "Reference intervals for carcinoembryonic antigen (CEA), CA125, MUC1, Alfa-foeto-protein (AFP), neuron-specific enolase (NSE) and CA19.9 from the NORIP study". Scandinavian Journal of Clinical and Laboratory Investigation 68 (8): 703–13. doi:10.1080/00365510802126836. PMID 18609108. 
  • Madendag Y, Col-Madendag I, Kanat-Pektas M, Danisman N (May 2009). "Predictive power of serum CA-125 and LDH in the outcome of first trimester pregnancies with human chorionic gonadotropin levels below discriminatory zone". Archives of Gynecology and Obstetrics 279 (5): 661–6. doi:10.1007/s00404-008-0798-x. PMID 18797897. 
  • Wang ML, Huang Q, Yang TX (Jul 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. 
  • Camlica H, Duranyildiz D, Tas F, Yasasever V (Dec 2008). "Statistical interpretation of CA125 and Bcl-2 in serum of patients with late stage ovarian cancer". American Journal of Clinical Oncology 31 (6): 585–8. doi:10.1097/COC.0b013e318174dbd2. PMID 19060592. 
  • Caffery B, Joyce E, Heynen ML, Jones L, Ritter R, Gamache DA, Senchyna M (2008). "MUC16 expression in Sjogren's syndrome, KCS, and control subjects". Molecular Vision 14: 2547–55. PMC 2613075. PMID 19122828. 
  • Prat A, Parera M, Adamo B, Peralta S, Perez-Benavente MA, Garcia A, Gil-Moreno A, Martinez-Palones JM, Baselga J, del Campo JM (Feb 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". Annals of Oncology 20 (2): 294–7. doi:10.1093/annonc/mdn601. PMID 18820245. 
  • de Larrea CF, Cibeira MT, Vallansot R, Colomo L, Bladé J (Oct 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, Kalayci H, Ibar Y (May 2009). "CA-125 and CRP are elevated in preeclampsia". Hypertension in Pregnancy 28 (2): 201–11. doi:10.1080/10641950802601187. PMID 19437230. 
  • Yu B, Xu PZ, Wang QW, Zhou H, Zhou HX (2009). "Clinical value of tumour specific growth factor (TSGF) and carbohydrate antigen-125 (CA-125) in carcinoma of the endometrium". The Journal of International Medical Research 37 (3): 878–83. doi:10.1177/147323000903700333. PMID 19589273. 
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