11 juli 2012: In Medline kunt een heleboel informatie lezen over de verschillende tumormarkers die worden gebruikt bij met name gynaecologische vormen van kanker zoals eierstokkanker: Gynecologic Tumor Markers Tumor Marker Overview. Author: Fazal Hussain, MD, MBBS; Chief Editor: Warner K Huh, MD  waaronder

Lysophosphatidic acid

Lysophosphatidic acid stimulates cancer cell proliferation, intracellular calcium release, and tyrosine phosphorylation, including mitogen-activated protein kinase activation. Lysophosphatidic acid has been shown to be a multifunctional signaling molecule in fibroblasts and other cells. It has been found in the ascitic fluid of patients with ovarian cancer and is associated with ovarian cancer cell proliferation. Further studies are needed to determine the role of this marker.

Een recente review studie uit 2011: Comparison of total plasma lysophosphatidic acid and serum CA-125 as a tumor marker in the diagnosis and follow-up of patients with epithelial ovarian cancer uit  Journal of Gynecological Oncology waar een gratis in te zien volledig studierapport een goed overzicht geeft van de waarde van LPA. Zie ook hieronder referentielijst van gerelateerde studies

2010 Dec 30;21(4):248-54. Epub 2010 Dec 31.

Comparison of total plasma lysophosphatidic acid and serum CA-125 as a tumor marker in the diagnosis and follow-up of patients with epithelial ovarian cancer.

Source

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Istanbul, Turkey.

Abstract

OBJECTIVE:

To evaluate the role of lysophosphatidic acid (LPA) as a tumor marker in diagnosis and follow-up of patients with epithelial ovarian cancer.

METHODS:

Eighty-seven epithelial ovarian cancer patients, 74 benign ovarian tumor patients, and 50 healthy women were enrolled in the study. Twenty-nine of 87 epithelial ovarian cancer patients were followed up for 6 cycles of paclitaxel-carboplatin chemotherapy. CA-125 and total plasma LPA levels were measured preoperatively and before each chemotherapy cycle.

RESULTS:

Preoperative total plasma LPA and serum CA-125 levels were significantly higher in patients with epithelial ovarian cancer compared to patients with benign ovarian tumors and healthy women. Cut-off value for LPA was determined as 1.3 µmol/L and sensitivity, specificity, positive predictive value and negative predictive value were 95%, 92%, 95% and 92%, respectively. Mean total plasma LPA level of 29 patients who received chemotherapy was 7.21±6.63 µmol/L preoperatively and 6.84±6.34 µmol/L, 6.34±5.92 µmol/L, 6.14±5.79 µmol/L, 5.86±5.68 µmol/L, 5.23±5.11 µmol/L and 5.21±5.32 µmol/L in measurements held just before the 1st, 2nd, 3rd, 4th, 5th and 6th chemotherapy cycles, respectively (ANOVA, p=0.832). Total plasma LPA levels decreased slightly with chemotherapy administration and there was a weak negative correlation (Spearman, r(s)=-0.151, p=0.034), compared to a significant negative correlation in CA-125 (Spearman, r(s)=-0.596, p<0.001).

CONCLUSION:

LPA is a better biomarker for diagnosis of epithelial ovarian cancer compared to CA-125. However, measurement of total plasma LPA levels during chemotherapy administration have no superiority to the serum CA-125 levels.

PMID:
21278887
PMCID:
PMC3026304

 

References

1. Aoki J, Taira A, Takanezawa Y, Kishi Y, Hama K, Kishimoto T, et al. Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J Biol Chem. 2002;277:48737–48744. [PubMed]
2. Eichholtz T, Jalink K, Fahrenfort I, Moolenaar WH. The bioactive phospholipid lysophosphatidic acid is released from activated platelets. Biochem J. 1993;291(Pt 3):677–680. [PMC free article] [PubMed]
3. Xu Y, Shen Z, Wiper DW, Wu M, Morton RE, Elson P, et al. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA. 1998;280:719–723. [PubMed]
4. Vogt W. Pharamacologically active acidic phospholipids and glycolipids. Biochem Pharmacol. 1963;12:415–420. [PubMed]
5. Xu Y, Gaudette DC, Boynton JD, Frankel A, Fang XJ, Sharma A, et al. Characterization of an ovarian cancer activating factor in ascites from ovarian cancer patients. Clin Cancer Res. 1995;1:1223–1232. [PubMed]
6. Mills GB, May C, McGill M, Roifman CM, Mellors A. A putative new growth factor in ascitic fluid from ovarian cancer patients: identification, characterization, and mechanism of action. Cancer Res. 1988;48:1066–1071. [PubMed]
7. Mills GB, May C, Hill M, Campbell S, Shaw P, Marks A. Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovarian adenocarcinoma cells. J Clin Invest. 1990;86:851–855. [PMC free article] [PubMed]
8. Xu Y, Fang XJ, Casey G, Mills GB. Lysophospholipids activate ovarian and breast cancer cells. Biochem J. 1995;309(Pt 3):933–940. [PMC free article] [PubMed]
9. Furui T, LaPushin R, Mao M, Khan H, Watt SR, Watt MA, et al. Overexpression of edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner. Clin Cancer Res. 1999;5:4308–4318. [PubMed]
10. Schwartz BM, Hong G, Morrison BH, Wu W, Baudhuin LM, Xiao YJ, et al. Lysophospholipids increase interleukin-8 expression in ovarian cancer cells. Gynecol Oncol. 2001;81:291–300. [PubMed]
11. Bast RC, Jr, Klug TL, Schaetzl E, Lavin P, Niloff JM, Greber TF, et al. Monitoring human ovarian carcinoma with a combination of CA 125, CA 19-9, and carcinoembryonic antigen. Am J Obstet Gynecol. 1984;149:553–559. [PubMed]
12. Brioschi PA, Irion O, Bischof P, Bader M, Forni M, Krauer F. Serum CA 125 in epithelial ovarian cancer: a longitudinal study. Br J Obstet Gynaecol. 1987;94:196–201. [PubMed]
13. Bast RC, Jr, Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981;68:1331–1337. [PMC free article] [PubMed]
14. Bast RC, Jr, Klug TL, St John E, Jenison E, Niloff JM, Lazarus H, et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med. 1983;309:883–887. [PubMed]
15. Paulsen T, Marth C, Kaern J, Nustad K, Kristensen GB, Trope C. Effects of paclitaxel on CA-125 serum levels in ovarian cancer patients. Gynecol Oncol. 2000;76:326–330. [PubMed]
16. Lavin PT, Knapp RC, Malkasian G, Whitney CW, Berek JC, Bast RC., Jr CA 125 for the monitoring of ovarian carcinoma during primary therapy. Obstet Gynecol. 1987;69:223–227. [PubMed]
17. Dalen A, Favier J, Burges A, Hasholzner U, de Bruijn HW, Dobler-Girdziunaite D, et al. Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients. Gynecol Oncol. 2000;79:444–450. [PubMed]
18. Bese T, Nomir SK. The importance of serum insulin-like growth factor-I level determination in the follow-up of patients with epithelial ovarian cancer. Eur J Gynaecol Oncol. 2001;22:372–376. [PubMed]
19. Westermann AM, Havik E, Postma FR, Beijnen JH, Dalesio O, Moolenaar WH, et al. Malignant effusions contain lysophosphatidic acid (LPA)-like activity. Ann Oncol. 1998;9:437–442. [PubMed]
20. Xiao YJ, Schwartz B, Washington M, Kennedy A, Webster K, Belinson J, et al. Electrospray ionization mass spectrometry analysis of lysophospholipids in human ascitic fluids: comparison of the lysophospholipid contents in malignant vs non-malignant ascitic fluids. Anal Biochem. 2001;290:302–313. [PubMed]
21. Baker DL, Morrison P, Miller B, Riely CA, Tolley B, Westermann AM, et al. Plasma lysophosphatidic acid concentration and ovarian cancer. JAMA. 2002;287:3081–3082. [PubMed]
22. Pozlep B, Meleh M, Kobal B, Verdenik I, Osredkar J, Kralj LZ, et al. Use of lysophosphatidic acid in the management of benign and malignant ovarian tumors. Eur J Gynaecol Oncol. 2007;28:394–399. [PubMed]
23. Sedláková I, Vávrová J, Tosner J, Hanousek L. Lysophosphatidic acid: an ovarian cancer marker. Eur J Gynaecol Oncol. 2008;29:511–514. [PubMed]
24. Yu S, Murph MM, Lu Y, Liu S, Hall HS, Liu J, et al. Lysophosphatidic acid receptors determine tumorigenicity and aggressiveness of ovarian cancer cells. J Natl Cancer Inst. 2008;100:1630–1642. [PMC free article] [PubMed]
25. Fang X, Gaudette D, Furui T, Mao M, Estrella V, Eder A, et al. Lysophospholipid growth factors in the initiation, progression, metastases, and management of ovarian cancer. Ann N Y Acad Sci. 2000;905:188–208. [PubMed]
26. Fang X, Schummer M, Mao M, Yu S, Tabassam FH, Swaby R, et al. Lysophosphatidic acid is a bioactive mediator in ovarian cancer. Biochim Biophys Acta. 2002;1582:257–264. [PubMed]
27. Goetzl EJ, Dolezalova H, Kong Y, Hu YL, Jaffe RB, Kalli KR, et al. Distinctive expression and functions of the type 4 endothelial differentiation gene-encoded G protein-coupled receptor for lysophosphatidic acid in ovarian cancer. Cancer Res. 1999;59:5370–5375. [PubMed]
28. Eder AM, Sasagawa T, Mao M, Aoki J, Mills GB. Constitutive and lysophosphatidic acid (LPA)-induced LPA production: role of phospholipase D and phospholipase A2. Clin Cancer Res. 2000;6:2482–2491. [PubMed]
29. Luquain C, Singh A, Wang L, Natarajan V, Morris AJ. Role of phospholipase D in agonist-stimulated lysophosphatidic acid synthesis by ovarian cancer cells. J Lipid Res. 2003;44:1963–1975. [PubMed]
30. Fang X, Yu S, Bast RC, Liu S, Xu HJ, Hu SX, et al. Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian cancer cells. J Biol Chem. 2004;279:9653–9661. [PubMed]
31. Hu YL, Tee MK, Goetzl EJ, Auersperg N, Mills GB, Ferrara N, et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. J Natl Cancer Inst. 2001;93:762–768. [PubMed]
32. Pustilnik TB, Estrella V, Wiener JR, Mao M, Eder A, Watt MA, et al. Lysophosphatidic acid induces urokinase secretion by ovarian cancer cells. Clin Cancer Res. 1999;5:3704–3710. [PubMed]
33. Symowicz J, Adley BP, Woo MM, Auersperg N, Hudson LG, Stack MS. Cyclooxygenase-2 functions as a downstream mediator of lysophosphatidic acid to promote aggressive behavior in ovarian carcinoma cells. Cancer Res. 2005;65:2234–2242. [PubMed]
34. Ren J, Xiao YJ, Singh LS, Zhao X, Zhao Z, Feng L, et al. Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells. Cancer Res. 2006;66:3006–3014. [PubMed]
35. Tanyi JL, Morris AJ, Wolf JK, Fang X, Hasegawa Y, Lapushin R, et al. The human lipid phosphate phosphatase-3 decreases the growth, survival, and tumorigenesis of ovarian cancer cells: validation of the lysophosphatidic acid signaling cascade as a target for therapy in ovarian cancer. Cancer Res. 2003;63:1073–1082. [PubMed]
36. Baker DL, Fujiwara Y, Pigg KR, Tsukahara R, Kobayashi S, Murofushi H, et al. Carba analogs of cyclic phosphatidic acid are selective inhibitors of autotaxin and cancer cell invasion and metastasis. J Biol Chem. 2006;281:22786–22793. [PubMed]

30 mei 2008: bron: uit internationale e-mailgroep werd ik hierop gewezen.

Het bloed aanvullend naast de CA 125 testen op LPA = lysophosphatidic acid kan vrouwen eerder duidelijkheid geven of zij eierstokkanker hebben of niet. Dit zou een belangrijke vondst kunnen zijn omdat beginnende eierstokkanker zelden of nooit wordt herkend omdat vrouwen dan meestal nog nergens last van hebben. Eierstokkanker wordt ook wel de stille moordenaar genoemd omdat het vaak pas geconstateerd wordt als de eierstokkanker al in een gervorderd stadium is. Meestal kan er dan niiet meer curatief behandeld worden. Slechts 25% van vrouwen met uitgezaaide eierstokkanker overleven de 5 jaar ondanks de reguliere behandelingen. Vrouwen waar eierstokkanker op tijd bij wordt gevonden en nog niet op afstand is uitgezaaid overleeft 95% de 5 jaar. Een goede diagnose test kan dus van levensbelang zijn.

In deze studie vergeleken onderzoekers de CA125 test  en LPA waarden bij patienten met eierstokkanker. Zij vonden dat LPA waarden accurater waren in het opsporen van eierstokkanker dan de CA125 waarden. Bv., 8 van de 9 stadium I eierstokkanker had verhoogde LPA waarden; slechts 2 van deze patienten had verhoogde CA125  waarden. Onder de 24 patienten met eierstokkanker stadium II, III, en IV had 100%  (24) verhoogde LPA waarden vergeleken met 54% (13) met verhoogde CA125 waarden.  Van vrouwen met een recidief van eierstokkanker, 100% (14/14) had verhoogde LPA waarden,  vergeleken met 86% (12/14) met verhoogde CA125 waarden. Overall 98% (47/48)  van de patienten met eierstokkanker had LPA waarden boven het gebruikelijke niveau vergeleken met 57%  (28/47) die verhoogde CA125 waarden hadden. De onderzoekers merkten wel op dat er grotere studies nodig zijn omdat er ook relatief veel valse positieve meldingen waren. Dus wel verhoogde LPA waarden maar toch geen eierstokkanker. Maar lijkt me een prima idee om als u twijfelt u gewoon ook op LPA te laten testen. Kost weinig tot niets extra en geeft dus blijkbaar meer zekerheid.

New Blood Test for Ovarian Cancer Shows Promise

Ovarian cancer is often described as a "silent" cancer because it
typically  causes no symptoms until it has spread quite extensively. The
outlook for  women who have localized ovarian cancer is very good, but
only 24 percent of the  cases are detected at this stage. Now, a new
test for ovarian cancer may  provide doctors with the ability to detect
these cancers much earlier, giving  women with the disease a better
chance at successful treatment.The new test  measures the levels of
lysophosphatidic acid (LPA) in the blood. Since LPA  stimulates the
growth of ovarian cancer cells, researchers speculated its presence  in
the blood may provide a good marker for the presence of ovarian
cancer."We believe the most important finding of this study is elevated
plasma LPA  levels were detected in patients with early-stage ovarian
cancer compared with  controls," noted the authors in the August 26,
1998 edition of the Journal of  the American Medical Association (JAMA).
Finding early-stage cancers would be  a great step forward. The
five-year survival rate for women with distant  spread of ovarian cancer
is about 25 percent. The outlook for women with  localized ovarian
cancer is much better-a 95 percent rate of survival beyond five
years.To perform the study, the researchers enrolled 165 women -- 48
with  ovarian cancer, 48 with no cancer, and 69 with other cancers or
benign  gynecological diseases, and measured their LPA levels.The
researchers found the LPA  blood levels of patients with ovarian cancer
were significantly higher than those  of the healthy control group. The
LPA levels were elevated in 9 of 10  patients with stage I ovarian
cancer and all patients with stages II, III, and IV  ovarian cancers.
However, among the healthy control groups, elevated LPA blood  levels
were found in 5 of 48 cases. Patients with other gynecological  cancers
also had higher LPA levels, as did some participants with benign
gynecological diseases, such as fibroid tumors.Comparison with CA125 The
CA125 blood test is currently used to help in diagnosis of ovarian
cancer and in detecting recurrence after treatment. However, CA125 is
not always  elevated in patients with early-stage disease and may be
elevated in certain  benign conditions, so it is not considered useful
as a routine screening test.  In this study, researchers compared CA125
and LPA levels in the patients  with ovarian cancer. They found that LPA
levels were more accurate in finding  ovarian cancers than were CA125
levels. For example, 8 of 9 stage I ovarian  cancers had elevated LPA
levels; only 2 of these patients had elevated CA125  levels. Among the
24 patients with stages II, III, and IV ovarian cancer, 100%  (24) had
elevated LPA levels compared to 54% (13) with elevated CA125 levels.  Of
women with recurrent ovarian cancer, 100% (14/14) had elevated LPA
levels,  compared to 86% (12/14) with elevated CA125 levels.Overall 98%
(47/48)  patients with ovarian cancer had LPA levels above the cut-off
compared to 57%  (28/47) who had elevated CA125 levels.Issues to be
addressed
> While these early findings are promising, the researchers cautioned that
 further studies will be needed to determine the general usefulness of
LPA as a  marker for ovarian cancer.The current study examined only a
small number of  women; future studies will need to incorporate many
more. Additionally, there  was a high rate of false positive tests.
Future studies will therefore need to  identify which other medical
conditions may affect the levels of LPA and  devise strategies will need
to be devised for reducing the false positive rate  before this test can
be used routinely. Finally, additional studies should be  performed to
assess how well LPA levels correlate with stage of disease and  disease
status to determine if it is a good marker for monitoring treatment,
progression, and recurrence of disease.
 


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