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Year 2025, Issue: Kabul Edilen Makaleler

Ceyhan Ceran Serdar , Şeyma Osmanlıoğlu

https://doi.org/10.31067/acusaglik.1539955

Abstract

References

  • 1. International Agency for Research on Cancer. Https://gco.iarc.fr/en.
  • 2. Mourits MJ, Bock GH de. European/U.S. Comparison and Contrasts in Ovarian Cancer Screening and Prevention in a High-Risk Population. Am Soc Clin Oncol Educ B 2017;37:124–7.
  • 3. De Angelis R, Sant M, Coleman MP, et al. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE-5-a population-based study. Lancet Oncol 2014;15(1):23–34.
  • 4. Kim JH, Cho HW, Park EY, et al. Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis. Int J Gynecol Cancer 2023;33(12):1913–20.
  • 5. Nassir M, Guan J, Luketina H, et al. The role of HE4 for prediction of recurrence in epithelial ovarian cancer patients-results from the OVCAD study. TUMOR Biol 2016;37(3):3009–16.
  • 6. Peng D, Xu T, Mason TJ, et al. A study of ovarian cancer biomarker amplification using ultrasound for early stage detection. Ultrasonics 2014;54(2):451–4.
  • 7. Bonifácio VDB. Ovarian Cancer Biomarkers: Moving Forward in Early Detection. Adv Exp Med Biol 2020;1219:355–63.
  • 8. Lecuru F, Sehouli J, Vergote IB, et al. Role of CA125 in patients included in the DESKTOP III/ENGOT-ov20 trial. Ann Oncol 2022;33:S809.
  • 9. Plotti F, Guzzo F, Schiro T, et al. Role of human epididymis protein 4 (HE4) in detecting recurrence in CA125 negative ovarian cancer patients. Int J Gynecol CANCER 2019;29(4):768–71.
  • 10. Bouchard D, Morisset D, Bourbonnais Y, et al. Proteins with whey-acidic-protein motifs and cancer. The lancet oncology. Lancet Oncol 2006;7(2):167–74.
  • 11. Piovano E, Attamante L, Macchi C, et al. The Role of HE4 in Ovarian Cancer Follow-up: A Review. Int J Gynecol Cancer 2014;24(8):1359–65.
  • 12. Ledermann JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24(SUPPL.6):vi24–32.
  • 13. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372.
  • 14. Hayden JA, Côté P, Bombardier C. Evaluation of the quality of prognosis studies in systematic reviews. Ann Intern Med 2006;144(6):427–37.
  • 15. Chen L, Yang X, Abasi X, et al. The diagnostic, prediction of postoperative recurrence and prognostic value of HE4 in epithelial ovarian cancer. J BUON 2018;23(2):428–32.
  • 16. Steffensen KD, Waldstrom M, Brandslund I, et al. Identification of high-risk patients by human epididymis protein 4levels during follow-up of ovarian cancer. Oncol Lett 2016;11(6):3967–74.
  • 17. Sun J, Cui X-W, Li Y-S, et al. The value of 18F-FDG PET/CT imaging combined with detection of CA125 and HE4 in the diagnosis of recurrence and metastasis of ovarian cancer. Eur Rev Med Pharmacol Sci 2020;24(13):7276–83.
  • 18. Uno M, Matsuo R, Maezawa N, et al. Evaluation of follow-up observation using human epididymis protein 4, a tumor marker, in patients with ovarian cancer. Obstet Gynecol Sci 2023;66(4):290–9.
  • 19. Gong Z, Han S, Zhang C, et al. Value of serum miR-21, HE4 and CA125 in surveillance for postoperative recurrent or metastatic ovarian cancer. PAKISTAN J Med Sci 2022;38(4, 2):939–45.
  • 20. Han JJ, Yu M, Houston N, et al. Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers. Gynecol Oncol 2011;120(1):5–10.
  • 21. Innao P, Pothisuwan M, Pengsa P. Does human epididymis protein 4 (HE4) have a role in prediction of recurrent epithelial ovarian cancer. Asian Pacific J Cancer Prev 2016;17(9):4483 – 4486.
  • 22. Kotowicz BU, Fuksiewicz M, Bidzinski M, et al. Measurement of HE4 six months after first-line treatment as optimal time in identifying patients at high risk of progression advanced ovarian cancer. Ginekol Pol 2022;93(11):910–5.
  • 23. Li R, Ma S, Zu Y, et al. Value of the risk of ovarian malignancy algorithm index in predicting the recurrence of epithelial ovarian cancer. Biomark Med 2022;16(14):1055–66.
  • 24. Rong Y, Li L. Early clearance of serum HE4 and CA125 in predicting platinum sensitivity and prognosis in epithelial ovarian cancer. J Ovarian Res 2021;14(1).
  • 25. Salminen L, Gidwani K, Grenman S, et al. HE4 in the evaluation of tumor load and prognostic stratification of high grade serous ovarian carcinoma. Acta Oncol (Madr) 2020;59(12):1461–8.
  • 26. Shen ZY, Shen AJ, Yang SL, et al. Combination of Sonographic Morphology Score and Tumor Markers for Detecting Postoperative Recurrent Pelvic Ovarian Carcinoma: Compared With MRI Assessment. ULTRASOUND Q 2019;35(1):45–53.
  • 27. Li J, Dowdy S, Tipton T, et al. HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn 2009;9(6):555–66.
  • 28. Ledermann JA, Matias-Guiu X, Amant F, et al. ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease. Ann Oncol 2024;35(3):248–66.
  • 29. Cao H, You D, Lan Z, et al. Prognostic value of serum and tissue HE4 expression in ovarian cancer: a systematic review with meta-analysis of 90 studies. Expert Rev Mol Diagn 2018;18(4):371–83.
  • 30. Gu P, Pan LL, Wu SQ, et al. CA 125, PET alone, PET-CT, CT and MRI in diagnosing recurrent ovarian carcinoma. A systematic review and meta-analysis. Eur J Radiol 2009;71(1):164–74.

Comparison of CA-125 and HE4 in ovarian cancer recurrence detection

Year 2025, Issue: Kabul Edilen Makaleler

Ceyhan Ceran Serdar , Şeyma Osmanlıoğlu

https://doi.org/10.31067/acusaglik.1539955

Abstract

Purpose: This study aims to comprehensively evaluate CA-125 and HE4 as predictors of ovarian cancer (OC) recurrence in the same patient population.
Methods: We systematically searched the WOS, PubMed, and Scopus databases on May 8, 2024, for studies investigating both tumor markers CA-125 and HE4 in the same patient population of ovarian cancer recurrence. We calculated pooled values of AUC, sensitivity, specificity, and univariate or multivariate hazard ratios (HR) for both tumor markers in serum using a random effects model and StataMP 17.0 software.
Results: Thirteen articles comprising 1026 patients satisfied the inclusion criteria. Liquid-biopsy-based HE4 and CA-125 measurements were both proven to have high predictive value for detecting OC recurrence with comparable AUC values (AUCHE4:0.78, 95% CI=0.73-0.83; AUCCA125:0.80, 95% CI=0.73-0.88). While sensitivity of HE4 tests was higher than their specificity (SensitivityHE4=80.7%; 95% CI=73-88.4; I²=77.05%; p<0.001; SpecificityHE4=77.8%; 95% CI=68.9-86.6; I²=83.88%; p<0.001) in detecting OC recurrence, specificity was comparably higher for CA-125 analyses (SensitivityCA-125=71.4%; 95% CI=60.2-82.7; I²=85,67%; p<0.001; SpecificityCA-125=94.5%; 95% CI=91.9-97.1; I²=10.64%; p=0.34). Pooled HR values indicate that increased values of HE4 and CA125 increase the risk for worse progression-free survival by 3.1 (95% CI=1.3–5.0, I²=0.00 %, p=0.38) and 2.4-fold (95% CI=1.3–3.5, I²=0.00 %, p=0.93) respectively. HE4 indicates worse overall survival (HR=6.9, CI=0.8–12.6, I²=0.00 %, p=0.7).
Conclusions: We suggest that HE4 is valuable as a recurrence tracker, with its higher sensitivity, while CA-125 can be used as a validator due to its higher specificity. Further prospective studies analyzing both biomarkers together are required for complete validation.

Keywords

ovarian cancer recurrence HE4 CA-125

Ethical Statement

No ethical approval and patient consent were required for this study as all of the included studies had recruited patients that provided informed consent.

Thanks

The authors sincerely thank Professor Muhittin Abdülkadir SERDAR for his invaluable insights and constructive feedback on this study.

References

  • 1. International Agency for Research on Cancer. Https://gco.iarc.fr/en.
  • 2. Mourits MJ, Bock GH de. European/U.S. Comparison and Contrasts in Ovarian Cancer Screening and Prevention in a High-Risk Population. Am Soc Clin Oncol Educ B 2017;37:124–7.
  • 3. De Angelis R, Sant M, Coleman MP, et al. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE-5-a population-based study. Lancet Oncol 2014;15(1):23–34.
  • 4. Kim JH, Cho HW, Park EY, et al. Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis. Int J Gynecol Cancer 2023;33(12):1913–20.
  • 5. Nassir M, Guan J, Luketina H, et al. The role of HE4 for prediction of recurrence in epithelial ovarian cancer patients-results from the OVCAD study. TUMOR Biol 2016;37(3):3009–16.
  • 6. Peng D, Xu T, Mason TJ, et al. A study of ovarian cancer biomarker amplification using ultrasound for early stage detection. Ultrasonics 2014;54(2):451–4.
  • 7. Bonifácio VDB. Ovarian Cancer Biomarkers: Moving Forward in Early Detection. Adv Exp Med Biol 2020;1219:355–63.
  • 8. Lecuru F, Sehouli J, Vergote IB, et al. Role of CA125 in patients included in the DESKTOP III/ENGOT-ov20 trial. Ann Oncol 2022;33:S809.
  • 9. Plotti F, Guzzo F, Schiro T, et al. Role of human epididymis protein 4 (HE4) in detecting recurrence in CA125 negative ovarian cancer patients. Int J Gynecol CANCER 2019;29(4):768–71.
  • 10. Bouchard D, Morisset D, Bourbonnais Y, et al. Proteins with whey-acidic-protein motifs and cancer. The lancet oncology. Lancet Oncol 2006;7(2):167–74.
  • 11. Piovano E, Attamante L, Macchi C, et al. The Role of HE4 in Ovarian Cancer Follow-up: A Review. Int J Gynecol Cancer 2014;24(8):1359–65.
  • 12. Ledermann JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24(SUPPL.6):vi24–32.
  • 13. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372.
  • 14. Hayden JA, Côté P, Bombardier C. Evaluation of the quality of prognosis studies in systematic reviews. Ann Intern Med 2006;144(6):427–37.
  • 15. Chen L, Yang X, Abasi X, et al. The diagnostic, prediction of postoperative recurrence and prognostic value of HE4 in epithelial ovarian cancer. J BUON 2018;23(2):428–32.
  • 16. Steffensen KD, Waldstrom M, Brandslund I, et al. Identification of high-risk patients by human epididymis protein 4levels during follow-up of ovarian cancer. Oncol Lett 2016;11(6):3967–74.
  • 17. Sun J, Cui X-W, Li Y-S, et al. The value of 18F-FDG PET/CT imaging combined with detection of CA125 and HE4 in the diagnosis of recurrence and metastasis of ovarian cancer. Eur Rev Med Pharmacol Sci 2020;24(13):7276–83.
  • 18. Uno M, Matsuo R, Maezawa N, et al. Evaluation of follow-up observation using human epididymis protein 4, a tumor marker, in patients with ovarian cancer. Obstet Gynecol Sci 2023;66(4):290–9.
  • 19. Gong Z, Han S, Zhang C, et al. Value of serum miR-21, HE4 and CA125 in surveillance for postoperative recurrent or metastatic ovarian cancer. PAKISTAN J Med Sci 2022;38(4, 2):939–45.
  • 20. Han JJ, Yu M, Houston N, et al. Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers. Gynecol Oncol 2011;120(1):5–10.
  • 21. Innao P, Pothisuwan M, Pengsa P. Does human epididymis protein 4 (HE4) have a role in prediction of recurrent epithelial ovarian cancer. Asian Pacific J Cancer Prev 2016;17(9):4483 – 4486.
  • 22. Kotowicz BU, Fuksiewicz M, Bidzinski M, et al. Measurement of HE4 six months after first-line treatment as optimal time in identifying patients at high risk of progression advanced ovarian cancer. Ginekol Pol 2022;93(11):910–5.
  • 23. Li R, Ma S, Zu Y, et al. Value of the risk of ovarian malignancy algorithm index in predicting the recurrence of epithelial ovarian cancer. Biomark Med 2022;16(14):1055–66.
  • 24. Rong Y, Li L. Early clearance of serum HE4 and CA125 in predicting platinum sensitivity and prognosis in epithelial ovarian cancer. J Ovarian Res 2021;14(1).
  • 25. Salminen L, Gidwani K, Grenman S, et al. HE4 in the evaluation of tumor load and prognostic stratification of high grade serous ovarian carcinoma. Acta Oncol (Madr) 2020;59(12):1461–8.
  • 26. Shen ZY, Shen AJ, Yang SL, et al. Combination of Sonographic Morphology Score and Tumor Markers for Detecting Postoperative Recurrent Pelvic Ovarian Carcinoma: Compared With MRI Assessment. ULTRASOUND Q 2019;35(1):45–53.
  • 27. Li J, Dowdy S, Tipton T, et al. HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn 2009;9(6):555–66.
  • 28. Ledermann JA, Matias-Guiu X, Amant F, et al. ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease. Ann Oncol 2024;35(3):248–66.
  • 29. Cao H, You D, Lan Z, et al. Prognostic value of serum and tissue HE4 expression in ovarian cancer: a systematic review with meta-analysis of 90 studies. Expert Rev Mol Diagn 2018;18(4):371–83.
  • 30. Gu P, Pan LL, Wu SQ, et al. CA 125, PET alone, PET-CT, CT and MRI in diagnosing recurrent ovarian carcinoma. A systematic review and meta-analysis. Eur J Radiol 2009;71(1):164–74.
There are 30 citations in total.

Details

Primary Language English
Subjects Obstetrics and Gynaecology
Journal Section Clinical Research
Authors

Ceyhan Ceran Serdar 0000-0002-2921-7030

Şeyma Osmanlıoğlu 0000-0003-4963-2685

Early Pub Date December 10, 2024
Publication Date
Submission Date August 28, 2024
Acceptance Date September 2, 2024
Published in Issue Year 2025Issue: Kabul Edilen Makaleler

Cite

EndNote Ceran Serdar C, Osmanlıoğlu Ş (December 1, 2024) Comparison of CA-125 and HE4 in ovarian cancer recurrence detection. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi Kabul Edilen Makaleler