Survivin and Vegf as Novel Biomarkers in Diagnosis of Endometriosis/ Survivin i vegf kao novi biomarkeri u dijagnostici endometrioze

Open access


Background: The aim of this study was to investigate the role of peripheral blood markers as additional diagnostic tools to transvaginal ultrasound (TVU) findings in the diagnosis of endometriosis.

Methods: This study included 40 patients undergoing laparoscopy for suspected endometriosis from January to December 2012. Preoperative levels of serum CA125, CA19-9, CEA and mRNA expression levels for survivin and VEGF were obtained. Real-time PCR was used to determine relative gene expression. A new diagnostic score was obtained by deploying the peripheral blood markers to the TVU findings. Statistical methods used were Chi-square, Fisher’s, Student’s t-test or the Mann - Whitney test.

Results: There was a statistically significant difference in serum CA125, survivin and VEGF levels in patients with endometriosis and those without endometriosis (p<0.001, p=0.025 and p=0.009, respectively). False negative TVU findings were noted in 3/13 patients (23.1%) with peritoneal endometriosis without ovaries involvement. High sensitivity (93.3%), specificity (90.0%), PPV (96.6%), NPV (81.8%) and accuracy (92.5%) were obtained for a diagnostic score based on TVU and significant peripheral blood markers (CA125, survivin and VEGF).

Conclusions: Determination of serum CA125, mRNA expression levels for survivin and VEGF along with TVU can contribute to higher accuracy of the noninvasive diagnostic tools for endometriosis.

1. Adamson GD. Endometriosis classification: an update.Curr Opin Obstet Gynecol 2011; 23: 213-20.

2. May KE, Villar J, Kirtley S, Kennedy SH, Becker CM.Endometrial alterations in endometriosis: a systematic review of putative biomarkers. Hum Reprod Update 2011; 17: 637-53.

3. Bedaiwy MA, Falcone T. Laboratory testing for endometriosis. Clin Chim Acta 2004; 340: 41-56.

4. Haas D, Chvatal R, Reichert B, Renner S, Shebl O, Binder H, et al. Endometriosis: a premenopausal disease? Age pattern in 42,079 patients with endometriosis. Arch Gynecol Obstet 2012; 286: 667-70.

5. Santulli P, Streuli I, Melonio I, Marcellin L, M’Baye M, Bititi A, et al. Increased serum cancer antigen-125 is a marker for severity of deep endometriosis. J Minim Invasive Gynecol 2015; 22(2): 275-84.

6. Londero AP, Calcagno A, Grassi T, Marzinotto S, Orsaria M, Beltrami CA, et al. Survivin, MMP-2, MT1-MMP, and TIMP-2: their impact on survival, implantation, and proliferation of endometriotic tissues. Virchows Arch 2012; 461(5): 589-99.

7. Kianpour M, Nematbakhsh M, Ahmadi SM, Jafarzadeh M, Hajjarian M, Pezeshki Z, et al. Serum and peritoneal fluid levels of vascular endothelial growth factor in women with endometriosis. Int J Fertil Steril 2013; 7 (2): 96-9.

8. Novaković I, Maksimović N, Pavlović A, Žarković M, Rovčanin B, Mirković D, Pekmezović T, Cvetković D.Introduction to molecular genetic diagnostics. J Med Biochem 2014; 33: 3-7.

9. Ozhan E, Kokcu A, Yanik K, Gunaydin M. Investigation of diagnostic potentials of nine different biomarkers in endometriosis. Eur J Obstet Gynecol Reprod Biol 2014; 178: 128-33.

10. Mabrouk M, Elmakky A, Caramelli E, Farina A, Mignemi G, Venturoli S, et al. Performance of peripheral (serum and molecular) blood markers for diagnosis of endometriosis. Arch Gynecol Obstet 2012; 285: 1307-12.

11. Watanabe A, Taniguchi F, Izawa M, Suou K, Uegaki T, Takai E, et al. The role of survivin in the resistance of endometriotic stromal cells to drug-induced apoptosis.Hum Reprod 2009; 24(12): 3172-9.

12. Zhang H, Li M, Zheng X, Sun Y, Wen Z, Zhao X. Endometriotic stromal cells lose the ability to regulate cell-survival signaling in endometrial epithelial cells in vitro. Mol Hum Reprod 2009; 15: 653-63.

13. Goteri G, Lucarini G, Pieramici T, Filosa A, Pugnaloni A, Montik N, et al. Endothelial cell surviving is involved in the growth of ovarian endometriotic cysts. Anticancer Res 2005; 25: 4313-8.

14. Fujino K, Ueda M, Takehara M, Futakuchi, H, Kanda K, Yamashita Y, et al. Transcriptional expression of survivin and its splice variants in endometriosis. Mol Hum Reprod 2006; 12(6): 383-8.

15. Baranov VS, Ivaschenko TE, Liehr T, Yarmolinskaya MI.Systems genetics view of endometriosis: a common complex disorder. Eur J Obstet Gynecol Reprod Biol 2015; 185: 59-65.

16. Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohí J, Simón C. The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril 1998; 70: 425-31.

17. Matalliotakis IM, Goumenou AG, Koumantakis GE, Neonaki MA, Koumantakis EE, Dionyssopoulou E, et al. Serum concentrations of growth factors in women with and without endometriosis: the action of anti-endometriosis medicines. Int Immunopharmacol 2003; 3: 81-9.

18. Robati M, Ghaderi A, Mehraban M, Shafizad A, Nasrolahi H, Mohammadianpanah M. Vascular endothelial growth factor (VEGF) improves the sensitivity of CA125 for differentiation of epithelial ovarian cancers from ovarian cysts.Arch Gynecol Obstet 2013; 288(4): 859-65.

19. Dai H, Zhao S, Xu L, Chen A, Dai S. Expression of Efp, VEGF and bFGF in normal, hyperplastic and malignant endometrial tissue. Oncol Rep 2010; 23(3): 795-9.

Journal of Medical Biochemistry

The Journal of Society of Medical Biochemists of Serbia

Journal Information

IMPACT FACTOR 2017: 1.378
5-year IMPACT FACTOR: 0.704

CiteScore 2017: 1.05

SCImago Journal Rank (SJR) 2017: 0.307
Source Normalized Impact per Paper (SNIP) 2017: 0.532

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 69 69 10
PDF Downloads 25 25 4