Assessment of diagnostic performance of HE4 and CA125, individually and combined in epithelial ovarian cancer screening
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20243583Keywords:
Human epididymis protein 4 (HE4), Epithelial ovarian cancer (EOC), Cancer antigen 125 (CA125), Benign diseaseAbstract
Background: Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies worldwide, often referred to as a "silent killer" due to its asymptomatic nature in the early stages. Proper diagnosis at early stage of Ovarian malignancy using biomarker is extremely important. The aim of this study was to evaluate the diagnostic accuracy of Human Epididymis Protein 4 (HE4) and Cancer Antigen 125 (CA125).
Methods: This descriptive observational study was conducted in Dhaka Medical College Hospital from January 2021 to December 2021. Data were collected using a pre-designed data collection sheet encompassing demographics, clinical examination, and investigation results. After obtaining informed written consent, clinical examinations and ultrasound of the abdomen were conducted, followed by the collection of venous blood samples.
Results: In our study predominant age group was 41-50 years (32.5%). Serum HE4 and CA125 concentrations were significantly higher in the ovarian cancer patients compared with those seen in patients with benign disease or in the healthy controls (p<0.05 in both). In patients with an adnexal mass, the area under the ROC curve was higher when the combination of the markers was used compared with use of CA125 only. Using ROMA, patients could be successfully classified into high- and low-risk group, with 57.7% sensitivity at a specificity of 63.9%.
Conclusions: These findings suggest that measuring serum HE4 concentrations along with CA125 concentrations may provide higher accuracy for detecting early stage of Epithelial ovarian cancer.
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References
Kristjansdottir B, Levan K, Partheen K, Sundfeldt K. Diagnostic performance of the biomarkers HE4 and CA125 in type I and type II epithelial ovarian cancer. Gynecologic oncology. 2013;1;131(1):52-8.
Ghasemi N, Ghobadzadeh S, Zahraei M, Mohammadpour H, Bahrami S, Ganje MB, et al. HE4 combined with CA125: favorable screening tool for ovarian cancer. Medical Oncology. 2014;31:1-6.
Jacob F, Meier M, Caduff R, Goldstein D, Pochechueva T, Hacker N, et al. No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting. Gynecologic oncology. 2011;1;121(3):487-91.
Wang J, Gao J, Yao H, Wu Z, Wang M, Qi J. Diagnostic accuracy of serum HE4, CA125 and ROMA in patients with ovarian cancer: a meta-analysis. Tumor Biology. 2014;35:6127-38.
Dochez V, Caillon H, Vaucel E, Dimet J, Winer N, Ducarme G. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. Journal of ovarian research. 2019;12:1-9.
Zheng LE, Qu JY, He F. The diagnosis and pathological value of combined detection of HE4 and CA125 for patients with ovarian cancer. Open Medicine. 2016;1;11(1):125-32.
Dayyani F, Uhlig S, Colson B, Simon K, Rolny V, Morgenstern D, et al. Diagnostic performance of risk of ovarian malignancy algorithm against CA125 and HE4 in connection with ovarian cancer: a meta-analysis. Int J Gynecologic Cancer. 2016;1:26.
Barr CE, Funston G, Jeevan D, Sundar S, Mounce LT, Crosbie EJ. The performance of HE4 alone and in combination with CA125 for the detection of ovarian cancer in an enriched primary care population. Cancers. 2022;24;14(9):2124.
Goff BA, Agnew K, Neradilek MB, Gray HJ, Liao JB, Urban RR. Combining a symptom index, CA125 and HE4 (triple screen) to detect ovarian cancer in women with a pelvic mass. Gynecologic oncology. 2017;147(2):291-5.
Zhao T, Hu W. CA125 and HE4. measurement tools for ovarian cancer. Gynecologic and obstetric investigation. 2016;29;81(5):430-5.
Van Gorp TI, Cadron I, Despierre E, Daemen A, Leunen K, Amant F, et al. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. Bri J Can. 2011;104(5):863-70.
Andersen MR, Goff BA, Lowe KA, Scholler N, Bergan L, Drescher CW, et al. Use of a Symptom Index, CA125, and HE4 to predict ovarian cancer. Gynecologic oncology. 2010;1;116(3):378-83.
Wang R, Li X, Li S, Fang S, Zhao C, Yang H, et al. Clinical value of O-RADS combined with serum CA125 and HE4 for the diagnosis of ovarian tumours. Acta Radiologica. 2023;64(2):821-8.
Barr CE, Njoku K, Owens GL, Crosbie EJ. Urine CA125 and HE4 for the detection of ovarian cancer in symptomatic women. Cancers. 2023;16;15(4):1256.
Moore RG, Brown AK, Miller MC. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008:108(2):402-8.
Havrilesky LJ, Whitehead CM, Rubatt JM, Cheek RL, Groelke J, He Q, et al. Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol Oncol. 2008;110:374–82.
Kim YM, Whang DM, Park J. Evaluation of the utility of serum human epididymis protein 4 in combination with CA 125 for detecting ovarian cancer: A prospective case-control study in a Korean population. J Gynecol Oncol. 2010;21(3),158-64.
Montagnana M, Lippi G, Ruzzenente O, Bresciani V, Danese E, Scevarolli S, et al. The utility of serum human epididymis protein 4 (HE4) in patients with a pelvic mass. J Clin Lab Anal 2009;23:331–5.
Hellstrom I, Raycraft J, Hayden- Ledbetter M, Ledbetter JA, Schummer M, Mcintosn M. et al. The HE4 (WFDC z) Protein is a biomarker for ovarian carcinoma. Cancer Res. 2003;63:3695-700.
Moore RG, McMeekin DS, Brown AK, DiSilvestro P, MillerMC, Allard WJ, et al. A novel multiple marker bioassay utilizingHE4 and CA125 for the prediction of ovarian cancer inpatients with a pelvic mass. Gynecol Oncol. 2009;112:40–6.
Kobel M, KallogerSE, Boyd N, McKinney S, Mehl E, Palmer C, et al. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med. 2008;5:1749-60.
