- Volume 15 Issue 1
Background and Purpose: Human epididymis protein 4 (HE4) has been suggested to be a novel biomarker of epithelial ovarian cancer (EOC). The present study aimed to evaluate and compare HE4 with the commonly used marker, carbohydrate antigen 125 (CA125), in prediction and therapy-monitoring of EOC. Patients and Methods: Serum HE4 concentrations from 123 ovarian cancer patients and 174 controls were measured by Roche electrochemiluminescent immunoassay (ECLIA). Risk of ovarian malignancy algorithm (ROMA) values were calculated and assessed. In addition, the prospects of HE4 detection for therapy-monitoring were evaluated in EOC patients. Results: The ROMA score could classify patients into high- and low-risk groups with malignancy. Indeed, lower serum HE4 was significantly associated with successful surgical therapy. Specifically, 38 patients with EOC exhibited a greater decline of HE4 compared with CA125. In contrast, elevation of HE4 better predicted recurrence (of 46, 11 patients developed recurrence, and with it increased HE4 serum concentrations) and a poor prognosis than CA125. Conclusions: This study suggests that serum HE4 levels are closely associated with outcome of surgical therapy and disease prognosis in Chinese EOC patients.
Ovarian cancer;biomarker;human epididymis protein 4;CA125;prognosis
- Siegel R, Naishadham D, Jemal A (2012). Cancer statistics, 2012. CA Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
- Ruggeri G, Bandiera E, Zanotti L, et al (2011). HE4 and epithelial ovarian cancer: comparison and clinical evaluation of two immunoassays and a combination algorithm. Clin Chim Acta, 412, 1447-53. https://doi.org/10.1016/j.cca.2011.04.028
- Rustin GJ, Vergote I, Eisenhauer E, et al (2011). Gynecological Cancer Intergroup. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer, 21, 419-23. https://doi.org/10.1097/IGC.0b013e3182070f17
- Schummer M, Drescher C, Forrest R, et al (2012). Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125. Gynecol Oncol, 125, 65-9. https://doi.org/10.1016/j.ygyno.2011.11.050
- Speeckaert MM, Speeckaert R, Delanghe JR (2013). Human epididymis protein 4 in cancer diagnostics: a promising and reliable tumor marker. Adv Clin Chem, 59, 1-21.
- Su ZL, Graybill WS, Zhu YS (2013). Detection and monitoring of ovarian cancer. Clinica Chimica Acta, 415, 341-5. https://doi.org/10.1016/j.cca.2012.10.058
- Mokhtar NM, Thevarajah M, Noorazmi MA, et al (2013). Human epididymis protein 4 reference intervals in a multiethnic Asian women population. Asian Pacific J Cancer Prev, 13, 6391-5. https://doi.org/10.7314/APJCP.2012.13.12.6391
- Macuks R, Baidekalna I, Donina S (2012). An ovarian cancer malignancy risk index composed of HE4, CA125, ultrasonographic score, and menopausal status: use in differentiation of ovarian cancers and benign lesions. Tumor Biol, 33, 1811-7. https://doi.org/10.1007/s13277-012-0440-1
- Maggino T, Gadducci A, D'Addario V, et al (1994). Prospective multicenter study on CA 125 in postmenopausal pelvic masses. Gynecol Oncol, 54, 117-23. https://doi.org/10.1006/gyno.1994.1179
- Miralles C, Orea M, Espana P, et al (2003). Cancer antigen 125 associated with multiple benign and malignant pathologies. Ann Surg Oncol, 10, 150-4. https://doi.org/10.1245/ASO.2003.05.015
- 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
- Moore RG, McMeekin DS, Brown AK, et al (2009). A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol, 112, 40-6. https://doi.org/10.1016/j.ygyno.2008.08.031
- Moore RG, Jabre-Raughley M, Brown AK, et al (2010). Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass. Am J Obstet Gynecol, 203, e221-6.
- Park Y, Kim Y, Lee EY (2012). Reference ranges for HE4 and CA125 in a large Asian population by automated assays and diagnostic performances for ovarian cancer. Int J Cancer, 130, 1136-44. https://doi.org/10.1002/ijc.26129
- 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
- Ferraro S, Braga F, Lanzoni M, et al (2013). Serum human epididymis protein 4 vs carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review. J Clin Pathol, 66, 273-81. https://doi.org/10.1136/jclinpath-2012-201031
- Devan SM, Pailoor J, Sthaneshwar P, et al (2013). Pattern of tissue expression of CA-125 and HE4 in primary epithelial ovarian tumours and correlation with serum CA-125 Levels. Asian Pac J Cancer Prev, 14, 4545-8. https://doi.org/10.7314/APJCP.2013.14.8.4545
- Drapkin R, Henning 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
- Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
- Havrilesky LJ, Whitehead CM, Rubatt JM, et al (2008). 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
- Hellstrom I, Raycraft J, Hayden-Ledbetter M, et al (2003). The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res, 63, 3695-700.
- Hynninen J, Auranen A, Dean K, et al (2011). Serum HE4 profile during primary chemotherapy of epithelial ovarian cancer. Int J Gynecol Cancer, 21, 1573-8. https://doi.org/10.1097/IGC.0b013e3182225509
- Lokshin AE (2012). The quest for ovarian cancer screening biomarkers: are we on the right road? Int J Gynecol Cancer, 22, S35-40. https://doi.org/10.1097/IGC.0b013e318251ccaa
- Lu RQ, Hu J, Guo L (2009). Evaluation of human epididymis protein 4 as a biomarker in patients with ovarian cancer. Chin J Lab Med, 32, 1379-83.
- Lu RQ, Guo L, Shen YH (2010). The roles of human epididymis protein 4 in patients with ovarian cancer. China Oncol, 20, 585-90.
- Bouchard D, Morisset D, Bourbonnais Y, et al (2006). Proteins with whey-acidic-protein motifs and cancer. Lancet Oncol, 7, 167-74. https://doi.org/10.1016/S1470-2045(06)70579-4
- Allard J, Somers E, Theil R, et al (2008). Use of a novel biomarker HE4 for monitoring patients with epithelial ovarian cancer. J Clin Oncol, 26, 5535.
- Andersen MR, Goff BA, Lowe KA, et al (2008). Combining a symptoms index with CA125 to improve detection of ovarian cancer. Cancer, 113, 484-9. https://doi.org/10.1002/cncr.23577
- Anton C, Carvalho FM, Oliveira EI, et al (2012). A Comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses. CLINICS, 67, 437-41. https://doi.org/10.6061/clinics/2012(05)06
- Overexpression of GOLPH3 protein is associated with worse prognosis in patients with epithelial ovarian cancer vol.35, pp.12, 2014, https://doi.org/10.1007/s13277-014-2411-1
- SIRT7 Exhibits Oncogenic Potential in Human Ovarian Cancer Cells vol.16, pp.8, 2015, https://doi.org/10.7314/APJCP.2015.16.8.3573
- The Establishment of an HE4-CLIA Method and the Combined Analysis of HE4 and CA125 in Ovarian Cancer vol.30, pp.5, 2016, https://doi.org/10.1002/jcla.21926
- Analysis of the gene expression profile in response to human epididymis protein 4 in epithelial ovarian cancer cells vol.36, pp.3, 2016, https://doi.org/10.3892/or.2016.4926
- Diagnostic and prognostic value of serum human epididymis protein 4 in patients with primary fallopian tube carcinoma vol.42, pp.10, 2016, https://doi.org/10.1111/jog.13053
- The role of novel biomarker HE4 in the diagnosis, prognosis and follow-up of ovarian cancer: a systematic review vol.17, pp.9, 2017, https://doi.org/10.1080/14737140.2017.1360138
- A new strategy for calculating the risk of ovarian malignancy algorithm (ROMA) vol.55, pp.8, 2017, https://doi.org/10.1515/cclm-2016-0582
- HE4 level in ascites may assess the ovarian cancer chemotherapeutic effect vol.11, pp.1, 2018, https://doi.org/10.1186/s13048-018-0402-3
Supported by : Science and Technology Commission of Shanghai Municipality