Serum biomarker profiles of interleukin-6, tumor necrosis factor alpha, matrix-metalloproteinase-2, and vascular endothelial growth factor in endometriosis staging

  • Wachyu Hadisaputra
  • Sandhy Prayudhana
DOI: https://doi.org/10.13181/mji.v22i2.532
Keywords: Endometriosis, interleukin-6, matrix-metalloproteinase-2, TNF-α, vascular endhothelial growth factor
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Abstract

Background: The focus of this study was to compare serum biomarkers: interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), matrix-metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in endometriosis stage I-II and stage III-IV.

Methods: This is a cross-sectional study. Forty endometriosis patients were diagnosed using laparoscopy procedure. Serum sample was taken before the surgery. The serum biomarkers (IL-6, TNF-α, MMP-2, and VEGF) were analyzed with ELISA method at the end of research. Mean of serum biomarkers in endometrosis stage I-II and stage III-IV were compared using unpaired t-test. Variables that show significant mean difference were tested using ROC measurement and the optimal cut-off point was determined.

Results: There was no significant difference in mean serum biomarkers level of IL-6, TNF-α, and MMP-2 between endometriosis stage I-II and stage III-IV (1.58 ± 0.78 vs 1.55 ± 0.98 pg/mL, 1.5 ± 0.47 vs 1.49 ± 0.29 pg/mL, and 152.04 ± 27.32 vs 140.98 ± 28.08 ng/mL, respectively). On the other hand, the comparison of VEGF level in endometriosis stage I-II and stage III-IV demonstrated significant difference (289.76 ± 188.13 vs 581.29 ± 512.85 pg/mL (p < 0.05)). Mean difference of VEGF had AUC of 74.5%. Optimal cut-off point for VEGF was 314.75 pg/mL with sensitivity 78.6% and specificity 69.2%.

Conclusion: This study showed that serum biomarkers of VEGF level (but not IL-6, TNF-α, and MMP-2) can be used to measure the degree of severity in endometriosis. VEGF level of 314.75 pg/mL represents the cut-off point between lower and higher stage of severity.

References

  1. Jacoeb TZ. Faktor Imunoendokrinologis dan seluler lingkungan mikro zalir peritoneal yang berperan pada infertilitas idiopatik wanita [dissertation]. Mount Pleasant (MI): Universitas Indonesia; 1990. Indonesian.

  2. Jacoeb TZ, Hadisaputra W. Penanganan endometriosis: panduan klinis dan algoritme. 1 ed. Jakarta: CV Sagung Seto; 2009. Indonesian.

  3. Lebovic DI, Muller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril 2001;75(1):1-10.

  4. Harada T, Iwabe T, Terakawa N. Role of cytokines in endometriosis. Fertil Steril 2001;76(1):1-10.

  5. Hendarto H. Profil kadar TNF-α, GDF-9 dan hyaluronan pada gangguan folikulogenesis sebagai gambaran penurunan kualitas oosit pasien endometriosis yang infertil [dissertation]. Mount Pleasant (MI): Universitas Airlangga; 2007. Indonesian.

  6. Oepomo TD. Peran interleukin-6 serta interleukin-8 dalam zalir peritoneal penderita infertilitas disertai endometriosis dalam proses apoptosis sel granulosa avarii yang patologis [dissertation]. Mount Pleasant (MI): Universitas Airlangga; 2003. Indonesian.

  7. Adiyono W. Dampak penambahan gonadotropin releasing hormon analog pada operasi laparoskopi terhadap manifestasi klinis, imunologis dan kualitas hidup penderita endometriosis [dissertation]. Mount Pleasant (MI); 2003. Indonesian.

  8. Stegmann BJ, Funk MJ, Sinaii N, et al. A logistic model for the prediction of endometriosis. Fertil Steril 2009;91(1):51-5.

  9. Hadisaputra W. Endometriosis: tinjauan perangai imunopatobiologi sebagai modalitas baru untuk menegakkan diagnosis endometriosis tanpa visualisasi Laparoskopi. Maj Obstet Ginekol Indones. 2007;31(3):180-4. Indonesian.

  10. ASRM PC. Endometriosis and infertility. Fertil Steril 2004;81(5):1441-6.

  11. Vignali M, Infantino M, Matrone R, et al. Endometriosis: novel etiopathogenetic concepts and clinical prespectives. Fertil Steril 2002;78(4):665-78.

  12. May K, Conduit-Hulbert S, Villar J, Kirtley S, Kennedy S, Becker C. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010;16(6):651-74.

  13. Gagne D, Rivard M, Page M, Shazand K, Hugo P, Gosselin D. Blood leukocyte subsets are modulated in patients with endometriosis. Fertil Steril 2003;80(1):43-53.

  14. Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, Agarwal A. Pathogenic mechanisms in endometriosis associated infertility. Fertil Steril 2008;90(2):247-57.

  15. Pitsos M, Kanakas N. The role of matrix metalloproteinases in the pathogenesis of endometriosis. Reprod Sci. 2009;16(8):717-26.

  16. Donnez J, Smoes P, Gillerot S, Casanas-Roux F, Nisolle M. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod. 1998;13(6):1686-90.

  17. Laschke MW, Menger MD. In vitro and in vivo approaches to study angiogenesis in the pathophysiology and therapy of endometriosis. Hum Reprod Update. 2007;13(4):331-42.

  18. Witz CA. Interleukin-6: another piece of the endometriosiscytokine puzzle. Fertil Steril 2000;73(2):212-4.

  19. Mihalyi A, Gevaert O, Kyama C, et al. Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers. Hum Reprod. 2010;25(3):654-64.

  20. Matalliotakis I, Goumenou A, Koumantakis G, et al. Serum concentration of growth factors in women with and without endometriosis: the action of anti-endometriosis medicines. Int Immunopharmacol. 2003;3(1):81-9.

  21. Xavier P, Belo L, Beires J, et al. Serum levels of VEGF and TNF-alpha and their association with C-reactive protein in patients with endometriosis. Arch Gynecol Obstet. 2006;273(4):227-31.

  22. Huang H-F, Hong L-H, Tan Y, Sheng J-Z. Matrix metalloproteinase 2 is associated with changes in steroid hormones in the sera and peritoneal fluid of patients with endometriosis. Fertil Steril 2004;81(5):1235-9.

  23. Maas JW, Groothuis PG, Dunselman GA, de Goeij AF, Struijker-Boudier HA, Evers JL. Development of endometriosis-like lesions after transplantation of human endometrial fragments onto the chick embryo chorioallantoic membrane. Hum Reprod. 2001;16(4):627-31.

  24. Martinez S, Garrido N, Coperias J, et al. Serum interleukin-6 levels are elevated in women with minimal mild endometriosis. Hum Reprod. 2007;22(3):836-42.

  25. Othman EE-DR, Hornung D, Hosam, et al. Serum cytokines as biomarker for nonsurgical prediction of endometriosis. Eur J Obstet Gynecol. 2007;137:240-6.

  26. Chae SJ, Kim H, Jee BC, Suh CS, Kim SH, Kim JG. Tumor necrosis factor (TNF)-TNF receptor gene polymorphisms and their serum levels in Korean women with endometriosis. Am J Reprod Immunol. 2008;60(5):432-9.

  27. McLaren J. Vascular endothelial growth factor and endometriotic angiogenesis. Hum Reprod Update. 2000;6:45-55.

  28. Cosin R, Estelles JG, Ramon L, et al. Influence of peritoneal fluid on the expression of angiogenic and proteolytic factors in cultures of endometrial cells from women with endometriosis. Hum Reprod. 2010;25(2):398-405.

  29. Gilabert-Estelles J, Ramon LA, Espana F, et al. Expression of angiogenic factors in endometriosis: relationship to fibrinolytic and metalloproteinase systems. Hum Reprod. 2007;22(8):2120-7.

  30. Garcia-Manero M, Santana GT, Alcazar JL. Relationship between microvascular density and expression of vascular endothelial growth factor in patients with ovarian endometriosis. J Womens Health (Larchmt). 2008;17(5):777-82.

  31. Pupo-Nogueira A, de Oliveira RM, Petta CA, Podgaec S, Dias JA, Jr., Abrao MS. Vascular endothelial growth factor concentrations in the serum and peritoneal fluid of women with endometriosis. Int J Gynaecol Obstet. 2007;99(1):33-7.

Published
2013-06-01
How to Cite
1.
Hadisaputra W, Prayudhana S. Serum biomarker profiles of interleukin-6, tumor necrosis factor alpha, matrix-metalloproteinase-2, and vascular endothelial growth factor in endometriosis staging. Med J Indones [Internet]. 2013Jun.1 [cited 2024Apr.26];22(2):76-2. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/532
Issue
Vol. 22 No. 2 (2013): May
Section
Clinical Research

Copyright (c) 2013 Wachyu Hadisaputra, Sandhy Prayudhana

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