Evaluation of follow-up observation using human epididymis protein 4, a tumor marker, in patients with ovarian cancer
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective We evaluated the usefulness of human epididymis protein 4 (HE4), a tumor marker, during and after treatment in patients with ovarian cancer (OC). Methods We included Japanese patients newly diagnosed with OC treated at the National Cancer Center Hospital between 2014 and 2021. The HE4 levels were measured in the serum stored during diagnosis. To evaluate the concordance between HE4 and the imaging results, we employed sequential pairs of blood sampling points and the results of imaging examinations. We compared the timing of the elevated HE4 levels, imaging diagnoses, and elevated cancer antigen 125 (CA125) levels in patients with recurrence. The Ethics Review Committee of our institution (2021-056) reviewed this study. Results Forty-eight patients with epithelial OC were eligible for enrollment. The sensitivity, specificity, and positive and negative predictive values of HE4 (criterion, 70 pmol/L) for disease progression during the follow-up period were 79.4%, 59.1%, 32.5%, and 92.0%, respectively (time point, n=317). We evaluated the relationship between HE4 and CA125 variability and disease status (recurrence or no recurrence). For recurrence, the sensitivity and negative predictive value of HE4 (criterion, 70 pmol/L), CA125 (criterion, 35 U/mL), and combination of HE4 and CA125 were 77.8%, 85.2%, and 92.6% and 75.0%, 82.6%, and 88.9%, respectively (n=48). Among the 27 patients who exhibited recurrence, 16 and nine showed earlier increased HE4 levels than the relevant imaging and CA125 levels, respectively. Conclusion HE4 may be a valuable marker for follow-up during and after OC therapy. A complementary role for HE4 and CA125 measurements was suggested for follow-up observations.
Abstract
Objective We evaluated the usefulness of human epididymis protein 4 (HE4), a tumor marker, during and after treatment in patients with ovarian cancer (OC). Methods We included Japanese patients newly diagnosed with OC treated at the National Cancer Center Hospital between 2014 and 2021. The HE4 levels were measured in the serum stored during diagnosis. To evaluate the concordance between HE4 and the imaging results, we employed sequential pairs of blood sampling points and the results of imaging examinations. We compared the timing of the elevated HE4 levels, imaging diagnoses, and elevated cancer antigen 125 (CA125) levels in patients with recurrence. The Ethics Review Committee of our institution (2021-056) reviewed this study. Results Forty-eight patients with epithelial OC were eligible for enrollment. The sensitivity, specificity, and positive and negative predictive values of HE4 (criterion, 70 pmol/L) for disease progression during the follow-up period were 79.4%, 59.1%, 32.5%, and 92.0%, respectively (time point, n=317). We evaluated the relationship between HE4 and CA125 variability and disease status (recurrence or no recurrence). For recurrence, the sensitivity and negative predictive value of HE4 (criterion, 70 pmol/L), CA125 (criterion, 35 U/mL), and combination of HE4 and CA125 were 77.8%, 85.2%, and 92.6% and 75.0%, 82.6%, and 88.9%, respectively (n=48). Among the 27 patients who exhibited recurrence, 16 and nine showed earlier increased HE4 levels than the relevant imaging and CA125 levels, respectively. Conclusion HE4 may be a valuable marker for follow-up during and after OC therapy. A complementary role for HE4 and CA125 measurements was suggested for follow-up observations.
참고문헌 (28)
- "Ovarian, fallopian tube, and peritoneal cancer: statistics" (2022)[URL]
- "Projection of cancer mortality and incidence in 2021" (2022)[URL]
- 하형인, "The incidence and survival of cervical, ovarian, and endometrial cancer in Korea, 1999-2017: Korea Central Cancer Registry", Obstetrics & Gynecology Science, 64(5), pp.444~453 (2021), 대한산부인과학회
- Kirchhoff C, "Molecular characterization of epididymal proteins", Rev Reprod, 3, pp.86~95 (1998)
- Bingle L, "The putative ovarian tumour marker gene HE4(WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms", Oncogene, 21, pp.2768~2773 (2002)
- Galgano MT, "Comprehensive analysis of HE4 expression in normal and malignant human tissues", Mod Pathol, 19, pp.847~853 (2006)
- Drapkin R, "Human epididymis protein 4(HE4)is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas", Cancer Res, 65, pp.2162~2169 (2005)
- Zhen S, "Comparison of serum human epididymis protein 4 and carbohydrate antigen 125 as markers in ovarian cancer : a meta-analysis", Mol Clin Oncol, 2, pp.559~566 (2014)
- Wang J, "Diagnostic accuracy of serum HE4, CA125 and ROMA in patients with ovarian cancer : a meta-analysis", Tumour Biol, 35, pp.6127~6138 (2014)
- Yang Z, "Clinical value of serum human epididymis protein 4 assay in the diagnosis of ovarian cancer : a meta-analysis", Onco Targets Ther, 6, pp.957~966 (2013)
- Hertlein L, "Human epididymis protein 4(HE4)in benign and malignant diseases", Clin Chem Lab Med, 50, pp.2181~2188 (2012)
- Omer B, "The diagnostic role of human epididymis protein 4 and serum amyloid-A in early-stage endometrial cancer patients", Tumour Biol, 34, pp.2645~2650 (2013)
- Jacobs I, "The CA 125 tumour-associated antigen : a review of the literature", Hum Reprod, 4, pp.1~12 (1989)
- Fujiwara H, "Evaluation of human epididymis protein 4(HE4)and risk of ovarian malignancy algorithm(ROMA)as diagnostic tools of type I and type II epithelial ovarian cancer in Japanese women", Tumour Biol, 36, pp.1045~1053 (2015)
- Capriglione S, "Ovarian cancer recurrence and early detection: may HE4 play a key role in this open challenge? A systematic review of literature", Med Oncol, 34, pp.164~ (2017)
- Hideki Tokunaga, "The 2020 Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer", Journal of Gynecologic Oncology, 32(2), pp.1~20 (2021), 대한부인종양학회[DOI]
- Sugiyama T, "Comparison of CA 125 assays with abdominopelvic computed tomography and transvaginal ultrasound in monitoring of ovarian cancer", Int J Gynaecol Obstet, 54, pp.251~256 (1996)
- Watanabe H, "New response evaluation criteria in solid tumours-revised RECIST guideline(version 1. 1)", Gan To Kagaku Ryoho, 36, pp.2495~2501 (2009)
- Plotti F, "Role of human epididymis protein 4(HE4)in detecting recurrence in CA125negative ovarian cancer patients", Int J Gynecol Cancer, 29, pp.768~771 (2019)
- Escudero JM, "Comparison of serum human epididymis protein 4 with cancer antigen 125 as a tumor marker in patients with malignant and nonmalignant diseases", Clin Chem, 57, pp.1534~1544 (2011)
- Nagy B Jr, "Elevated human epididymis protein 4concentrations in chronic kidney disease", Ann Clin Biochem, 49, pp.377~380 (2012)
- Schummer M, "Evaluation of ovarian cancer remission markers HE4, MMP7 and mesothelin by comparison to the established marker CA125", Gynecol Oncol, 125, pp.65~69 (2012)
- Manganaro L, "Serum HE4 levels combined with CE CT imaging improve the management of monitoring women affected by epithelial ovarian cancer", Oncol Rep, 30, pp.2481~2487 (2013)
- Hatzipetros I, "Investigating the clinical potential for 14-3-3 zeta protein to serve as a biomarker for epithelial ovarian cancer", J Ovarian Res, 6, pp.79~ (2013)
- Innao P, "Does human epididymis protein 4(HE4)have a role in prediction of recurrent epithelial ovarian cancer", Asian Pac J Cancer Prev, 17, pp.4483~4486 (2016)
- Berger Y, "Elevations of serum CA-125 predict severity of acute appendicitis in males", ANZ J Surg, 86, pp.260~263 (2016)
- Miralles C, "Cancer antigen 125 associated with multiple benign and malignant pathologies", Ann Surg Oncol, 10, pp.150~154 (2003)
- Rustin GJ, "Use of CA-125 to define progression of ovarian cancer in patients with persistently elevated levels", J Clin Oncol, 19, pp.4054~4057 (2001)