DOI QR코드

DOI QR Code

Urinary Concentrations of Human Epidydimis Secretory Protein 4 (He4) in The Diagnosis of Ovarian Cancer: A Case-Control Study

  • Macuks, Ronalds (Department of Gynecology and Obstetrics of Riga Stradins University) ;
  • Baidekalna, Ieva (Department of Gynecology and Obstetrics of Riga Stradins University) ;
  • Donina, Simona (Department of Immunology of Riga Eastern Clinical University Hospital)
  • 발행 : 2012.09.30

초록

Objective: To analyze differential diagnostic accuracy of urinary human epidydimis secretory protein 4 (HE4) in patients with ovarian tumors. Materials and methods: In the case-control study 23 patients with ovarian cancer, 37 patients with benign ovarian tumors and 18 women in the control group were included. Serum CA125 values and urinary concentrations of HE4were assessed quantitatively. Urinary creatinine concentrations and glomerular filtration rate were also determined and used to calculate ratios to HE4. Results: Higher urinary HE4 concentrations were observed in patients with late stage ovarian cancer (p=0.001) and also in patients with early stage ovarian cancer when compared to patients with benign ovarian tumors (p=0.044). On analysis where all ovarian cancer patients were included, higher diagnostic accuracy was observed with calculated ratio of HE4 to glomerular filtration rate (GFR) to unchanged urinary HE4 concentrations -AUC 0.861 vs. 0.858. When discriminatory accuracy was calculated for urinary HE4/GFR ratio and unchanged urinary HE4 concentrations, the last demonstrated a higher area under the curve - 0.701 vs. 0.602. The urinary HE4/creatinine ratio had lower discriminatory characteristics than unchanged concentrations of urinary HE4. However, HE4 serum concentration was more accurate for discrimination of patients with benign and malignant ovarian tumors when compared to urinary HE4 and CA125 in sera (AUCs were 0.868 for serum HE4 and 0.856 and 0.653 for urinary HE4 and CA125, respectively). Conclusions: Ovarian cancer patients have higher urinary concentrations of human epidydimis secretory protein 4 than patients with benign ovarian tumors. Urinary HE4 has comparable discriminatory accuracy with serum HE4 for benign and malignant ovarian tumors and can be recommended as a non-invasive ovarian cancer risk assessment method.

키워드

참고문헌

  1. Boshell M, Lalani EN, Pemberton L ,et al (1992). The product of the human MUC1 gene when secreted by mouse cells transfected with the full-length cDNA lacks the cytoplasmic tail. Biochem Biophys Res Commun, 185, 1-8. https://doi.org/10.1016/S0006-291X(05)80946-5
  2. Davies DF, Shock NW (1950). Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest, 29, 496-507. https://doi.org/10.1172/JCI102286
  3. Drapkin R, von Horsten H, Lin Y, et al (2005). Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res, 65, 2162-9. https://doi.org/10.1158/0008-5472.CAN-04-3924
  4. Guo L. Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cells proliferation and motility. 2nd World Congress on Biomarkers & Clinical Research, 12-14 September 2011, Baltimore Marriott Waterfront, USA.
  5. Havrilesky LJ, Whitehead CM, Rubatt JM, et al (2008). Berchuck A. Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol Oncol, 110, 374-82. https://doi.org/10.1016/j.ygyno.2008.04.041
  6. Hellstrom I, Heagerty PJ, Swisher EM, et al (2010). Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms. Cancer Lett, 296, 43-8. https://doi.org/10.1016/j.canlet.2010.03.013
  7. Hellstrom I, Raycraft J, Hayden-Ledbetter M, et al (2003). The HE4 (WFDC2) protein is a biomarker for ovarian cancer. Cancer Res, 63, 3695-3700.
  8. Huhtinen K, Suvitie P, Hiissa J, (2009). Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer, 100, 1315-9. https://doi.org/10.1038/sj.bjc.6605011
  9. Kirchhoff C, Osterhoff C, Pera I, Schroter S (1998). Function of human epididymal proteins in sperm maturation. Andrologia, 30, 225-32.
  10. Ligtenberg MJ, Kruijshaar L, Buijs F, et al (1992). Cellassociated episialin is a complex containing two proteins derived from a common precursor. J Biol Chem, 267, 6171-7.
  11. Moore R, Brown A, Miller M,et al (2008). The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol, 108, 402-8. https://doi.org/10.1016/j.ygyno.2007.10.017
  12. Moore RG, Brown AK, Miller MC, et al (2008). The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol, 108, 402-8. https://doi.org/10.1016/j.ygyno.2007.10.017
  13. Partheen K, Kristjansdottir B, Sundfeldt K (2011). Evaluation of ovarian cancer biomarkers HE4 and CA-125 in women presenting with a suspicious cystic ovarian mass. J Gynecol Oncology, 22, 244-52. https://doi.org/10.3802/jgo.2011.22.4.244
  14. Rosen DG, Wang L, Atkinson JN, et al (2005). Potential markers that complement expression of CA125 in epithelial ovarian cancer. Gynecol Oncol, 99, 267-77. https://doi.org/10.1016/j.ygyno.2005.06.040
  15. Schummer M, Ng WV, Bumgarner RE, et al (1999).Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene, 238, 375-85. https://doi.org/10.1016/S0378-1119(99)00342-X
  16. Van Gorp T, Cadron I, Despierre E, et al (2011). HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the risk of ovarian malignancy algorithm. Br J Cancer, 104, 863-70. https://doi.org/10.1038/sj.bjc.6606092
  17. Yin BW, Lloyd KO (2001). Molecular cloning of the CA125 ovarian cancer antigen: Identification as a new mucin, MUC16. J Biol Chem, 276, 27371-5. https://doi.org/10.1074/jbc.M103554200

피인용 문헌

  1. Discovery and validation of urinary metabotypes for the diagnosis of hepatocellular carcinoma in West Africans vol.60, pp.4, 2014, https://doi.org/10.1002/hep.27264
  2. HE4-test of urine and body fluids for diagnosis of gynecologic cancer vol.17, pp.3, 2017, https://doi.org/10.1080/14737159.2017.1282824
  3. Diagnostic value of urinary-to-serum human epididymis protein 4 ratio in ovarian cancer vol.7, pp.1, 2017, https://doi.org/10.3892/br.2017.913