Human Epididymis Protein 4 in Early Diagnosis of Endometrial Cancer: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 ZHANGJing ¹ , WANGYu-juan ¹ , HUOJun-ling ¹ ,  WANGZan-hong ²

1. Shanxi Medical University, Taiyuan 030001, China;
2. Department of Gynecology, Shanxi Academy of Medical Sciences, Hospital of Shanxi Medical University, Taiyuan 030032, China;

Corresponding author：

WANGZan-hong, Email: wangzanhong@126.com

Keywords：

Human epididymis protein 4; Endometrial cancer; Tumor marker; Systematic review; Meta-analysis; Diagnostic test

DOI：

10.7507/1672-2531.20140013

Video：

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Objective To systematically review the value of human epididymis protein 4 (HE4) in early diagnosis of endometrial cancer. Methods Databases including The Cochrane Library (Issue 1, 2013), PubMed, MEDLINE (Ovid), CNKI, CBM and WanFang Data were electronically searched for relevant studies on HE4 versus the golden standard (pathological examination) in the diagnosis of endometrial cancer from inception to April 2013. Meanwhile, relevant journals were also manually searched. Two reviewers independently screened literature according to the inclusion and exclusion criteria, and evaluated the included studies using the QUADAS items. Then, meta-analysis was performed using RevMan 5.1 and Meta-DiSc 1.0. Results Finally, a total of 16 studies involving 2 299 women (1 088 endometrial cancer patients diagnosed according to the golden standard, of which, 504 with benign uterine disease and 707 with normal cervical) were included. The results of meta-analysis showed that, as for HE4 in early diagnosis of endometrial cancer (SEN=57%, 95%CI 0.54 to 0.60; SPE=92%, 95%CI 0.91 to 0.94; +LR=6.92, 95%CI 5.00 to 9.58;-LR=0.46, 95%CI 0.39 to 0.55; DOR=18.38, 95%CI 12.21 to 27.69; AUC=0.881 7). Conclusion The current study indicates that serum HE4 is more sensitive and low specific when applied in patients with endometrial cancer, which is worth of being used in clinic. Due to the limitation of low quality of the included studies, more high quality trials are required to verify the above conclusion.

Citation： ZHANGJing, WANGYu-juan, HUOJun-ling, WANGZan-hong. Human Epididymis Protein 4 in Early Diagnosis of Endometrial Cancer: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2014, 14(1): 72-78. doi: 10.7507/1672-2531.20140013 Copy

1.	Drapkin R, von Horsten HH, Lin Y, et al. Human epididymis protein 4(HE4)is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res, 2005, 65(6):2162-2169.
2.	Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS:a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol, 2003, 3:25.
3.	Moore RG, Brown AK, Miller MC, et al. Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus. Gynecol Oncol, 2008, 110(2):196-201.
4.	张雪玉, 杨彩虹, 吕娟.子宫内膜癌患者血清中HE4、YKL-40的表达及临床意义.现代妇产科进展, 2011, 20(5):377-380.
5.	梁莹莹, 李宝香.血清人附睾分泌蛋白4表达水平诊断子宫内膜癌的价值初探.中国老年保健医学, 2011, 9(3):10-12.
6.	胡娟, 江铭磊, 郭林, 等.血清肿瘤标志物HE4检测对子宫内膜癌诊治的临床应用.现代免疫学, 2012, 32(2):164-167.
7.	吴飞, 周慧芹, 崔满华.联合检测CA125与HE4在子宫内膜癌诊断中的价值.中国妇幼保健, 2011, 26(10):1559-1561.
8.	王小娇, 李惠新.上皮性卵巢癌血清OPN、HE4和CA125水平的检测及临床意义.兰州:兰州大学, 2011.
9.	杨彩虹, 徐永辉, 张雪.人附睾蛋白4在子宫内膜癌组织及血清中的表达及临床意义.中国肿瘤临床, 2011, 38(9):516-519.
10.	Bignotti E, Ragnoli M, Zanotti L, et al. Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients.Br J Cancer, 2011, 104(9):1418-1425.
11.	杨胜晗, 李群. HE4在子宫内膜癌患者血清中的表达其与CA125联合检测的临床意义.安徽:蚌埠医学院, 2011.
12.	赵灵琴, 陈曦, 陈鲁.人附睾分泌蛋白4和CA125联合检测在子宫内膜恶性肿瘤与子宫良性肿瘤鉴别诊断中的价值.中国癌症杂志, 2012, 22(11):820-823.
13.	简慧秋, 徐春林.尿液人附睾蛋白4在卵巢癌、子宫内膜癌诊断和鉴别诊断中的意义.河北:河北医科大学, 2012.
14.	李京华, 张铁, 王萍, 等. HE4、CA125在子宫内膜癌辅助诊断中的作用.中华医学会第七次全国中青年检验医学学术会议会议论文集.江苏, 2012-05-03.
15.	张爱敏, 张鹏.血清人附睾分泌蛋白E4和CA125联合检测对子宫内膜癌诊断的临床价值.中华妇产科杂志, 2012, 47(2):125-128.
16.	马荣, 耿晓星, 唐丽萍, 等.人附睾分泌蛋白4检测对子宫内膜癌的诊断及预后的意义.临床肿瘤学杂志, 2011, 16(9):790-793.
17.	Angioli R, Plotti F, Capriglione S, et al. The role of novel biomarker HE4 in endometrial cancer:a case control prospective study. Tumor Biol, 2013, 34:571-576.
18.	於王骐, 洪理泉, 刘战峰.血清HE4检测在卵巢癌和子宫内膜癌诊断中的应用.中国卫生检验杂志, 2013, 23(2):416-419.
19.	Kirchhoff C, Habben I, Ivell R, et al. A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod, 1991, 45(2):350-357.
20.	Bingle L, Singleton V, Bingle CD. The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms. Oncogene, 2002, 21(17):2768-2773.
21.	Hellström I, Raycraft J, Hayden-Ledbetter M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res, 2003, 63(13):3695-3700.
22.	Montagnana M, Lippi G, Ruzzenente O, et al. The utility of serum human epididymis protein 4 (HE4) in patients with a pelvic mass. J Clin Lab Anal, 2009, 23(5):331-335.
23.	Galgano MT, Hampton GM, Frierson HF Jr. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol, 2006, 19(6):847-853.

1. Drapkin R, von Horsten HH, Lin Y, et al. Human epididymis protein 4(HE4)is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res, 2005, 65(6):2162-2169.
2. Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS:a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol, 2003, 3:25.
3. Moore RG, Brown AK, Miller MC, et al. Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus. Gynecol Oncol, 2008, 110(2):196-201.
4. 张雪玉, 杨彩虹, 吕娟.子宫内膜癌患者血清中HE4、YKL-40的表达及临床意义.现代妇产科进展, 2011, 20(5):377-380.
5. 梁莹莹, 李宝香.血清人附睾分泌蛋白4表达水平诊断子宫内膜癌的价值初探.中国老年保健医学, 2011, 9(3):10-12.
6. 胡娟, 江铭磊, 郭林, 等.血清肿瘤标志物HE4检测对子宫内膜癌诊治的临床应用.现代免疫学, 2012, 32(2):164-167.
7. 吴飞, 周慧芹, 崔满华.联合检测CA125与HE4在子宫内膜癌诊断中的价值.中国妇幼保健, 2011, 26(10):1559-1561.
8. 王小娇, 李惠新.上皮性卵巢癌血清OPN、HE4和CA125水平的检测及临床意义.兰州:兰州大学, 2011.
9. 杨彩虹, 徐永辉, 张雪.人附睾蛋白4在子宫内膜癌组织及血清中的表达及临床意义.中国肿瘤临床, 2011, 38(9):516-519.
10. Bignotti E, Ragnoli M, Zanotti L, et al. Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients.Br J Cancer, 2011, 104(9):1418-1425.
11. 杨胜晗, 李群. HE4在子宫内膜癌患者血清中的表达其与CA125联合检测的临床意义.安徽:蚌埠医学院, 2011.
12. 赵灵琴, 陈曦, 陈鲁.人附睾分泌蛋白4和CA125联合检测在子宫内膜恶性肿瘤与子宫良性肿瘤鉴别诊断中的价值.中国癌症杂志, 2012, 22(11):820-823.
13. 简慧秋, 徐春林.尿液人附睾蛋白4在卵巢癌、子宫内膜癌诊断和鉴别诊断中的意义.河北:河北医科大学, 2012.
14. 李京华, 张铁, 王萍, 等. HE4、CA125在子宫内膜癌辅助诊断中的作用.中华医学会第七次全国中青年检验医学学术会议会议论文集.江苏, 2012-05-03.
15. 张爱敏, 张鹏.血清人附睾分泌蛋白E4和CA125联合检测对子宫内膜癌诊断的临床价值.中华妇产科杂志, 2012, 47(2):125-128.
16. 马荣, 耿晓星, 唐丽萍, 等.人附睾分泌蛋白4检测对子宫内膜癌的诊断及预后的意义.临床肿瘤学杂志, 2011, 16(9):790-793.
17. Angioli R, Plotti F, Capriglione S, et al. The role of novel biomarker HE4 in endometrial cancer:a case control prospective study. Tumor Biol, 2013, 34:571-576.
18. 於王骐, 洪理泉, 刘战峰.血清HE4检测在卵巢癌和子宫内膜癌诊断中的应用.中国卫生检验杂志, 2013, 23(2):416-419.
19. Kirchhoff C, Habben I, Ivell R, et al. A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod, 1991, 45(2):350-357.
20. Bingle L, Singleton V, Bingle CD. The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms. Oncogene, 2002, 21(17):2768-2773.
21. Hellström I, Raycraft J, Hayden-Ledbetter M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res, 2003, 63(13):3695-3700.
22. Montagnana M, Lippi G, Ruzzenente O, et al. The utility of serum human epididymis protein 4 (HE4) in patients with a pelvic mass. J Clin Lab Anal, 2009, 23(5):331-335.
23. Galgano MT, Hampton GM, Frierson HF Jr. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol, 2006, 19(6):847-853.

Chinese Journal of Evidence-Based Medicine

Human Epididymis Protein 4 in Early Diagnosis of Endometrial Cancer: A Systematic Review

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