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.	張雪玉, 楊彩虹, 呂娟.子宮內膜癌患者血清中HE4、YKL-40的表達及臨床意義.現代婦產科進展, 2011, 20(5):377-380.
5.	梁瑩瑩, 李寶香.血清人附睪分泌蛋白4表達水平診斷子宮內膜癌的價值初探.中國老年保健醫學, 2011, 9(3):10-12.
6.	胡娟, 江銘磊, 郭林, 等.血清腫瘤標志物HE4檢測對子宮內膜癌診治的臨床應用.現代免疫學, 2012, 32(2):164-167.
7.	吳飛, 周慧芹, 崔滿華.聯合檢測CA125與HE4在子宮內膜癌診斷中的價值.中國婦幼保健, 2011, 26(10):1559-1561.
8.	王小嬌, 李惠新.上皮性卵巢癌血清OPN、HE4和CA125水平的檢測及臨床意義.蘭州:蘭州大學, 2011.
9.	楊彩虹, 徐永輝, 張雪.人附睪蛋白4在子宮內膜癌組織及血清中的表達及臨床意義.中國腫瘤臨床, 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.	楊勝晗, 李群. HE4在子宮內膜癌患者血清中的表達其與CA125聯合檢測的臨床意義.安徽:蚌埠醫學院, 2011.
12.	趙靈琴, 陳曦, 陳魯.人附睪分泌蛋白4和CA125聯合檢測在子宮內膜惡性腫瘤與子宮良性腫瘤鑒別診斷中的價值.中國癌癥雜志, 2012, 22(11):820-823.
13.	簡慧秋, 徐春林.尿液人附睪蛋白4在卵巢癌、子宮內膜癌診斷和鑒別診斷中的意義.河北:河北醫科大學, 2012.
14.	李京華, 張鐵, 王萍, 等. HE4、CA125在子宮內膜癌輔助診斷中的作用.中華醫學會第七次全國中青年檢驗醫學學術會議會議論文集.江蘇, 2012-05-03.
15.	張愛敏, 張鵬.血清人附睪分泌蛋白E4和CA125聯合檢測對子宮內膜癌診斷的臨床價值.中華婦產科雜志, 2012, 47(2):125-128.
16.	馬榮, 耿曉星, 唐麗萍, 等.人附睪分泌蛋白4檢測對子宮內膜癌的診斷及預后的意義.臨床腫瘤學雜志, 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.	於王騏, 洪理泉, 劉戰峰.血清HE4檢測在卵巢癌和子宮內膜癌診斷中的應用.中國衛生檢驗雜志, 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.	Hellstr?m 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. 張雪玉, 楊彩虹, 呂娟.子宮內膜癌患者血清中HE4、YKL-40的表達及臨床意義.現代婦產科進展, 2011, 20(5):377-380.
5. 梁瑩瑩, 李寶香.血清人附睪分泌蛋白4表達水平診斷子宮內膜癌的價值初探.中國老年保健醫學, 2011, 9(3):10-12.
6. 胡娟, 江銘磊, 郭林, 等.血清腫瘤標志物HE4檢測對子宮內膜癌診治的臨床應用.現代免疫學, 2012, 32(2):164-167.
7. 吳飛, 周慧芹, 崔滿華.聯合檢測CA125與HE4在子宮內膜癌診斷中的價值.中國婦幼保健, 2011, 26(10):1559-1561.
8. 王小嬌, 李惠新.上皮性卵巢癌血清OPN、HE4和CA125水平的檢測及臨床意義.蘭州:蘭州大學, 2011.
9. 楊彩虹, 徐永輝, 張雪.人附睪蛋白4在子宮內膜癌組織及血清中的表達及臨床意義.中國腫瘤臨床, 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. 楊勝晗, 李群. HE4在子宮內膜癌患者血清中的表達其與CA125聯合檢測的臨床意義.安徽:蚌埠醫學院, 2011.
12. 趙靈琴, 陳曦, 陳魯.人附睪分泌蛋白4和CA125聯合檢測在子宮內膜惡性腫瘤與子宮良性腫瘤鑒別診斷中的價值.中國癌癥雜志, 2012, 22(11):820-823.
13. 簡慧秋, 徐春林.尿液人附睪蛋白4在卵巢癌、子宮內膜癌診斷和鑒別診斷中的意義.河北:河北醫科大學, 2012.
14. 李京華, 張鐵, 王萍, 等. HE4、CA125在子宮內膜癌輔助診斷中的作用.中華醫學會第七次全國中青年檢驗醫學學術會議會議論文集.江蘇, 2012-05-03.
15. 張愛敏, 張鵬.血清人附睪分泌蛋白E4和CA125聯合檢測對子宮內膜癌診斷的臨床價值.中華婦產科雜志, 2012, 47(2):125-128.
16. 馬榮, 耿曉星, 唐麗萍, 等.人附睪分泌蛋白4檢測對子宮內膜癌的診斷及預后的意義.臨床腫瘤學雜志, 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. 於王騏, 洪理泉, 劉戰峰.血清HE4檢測在卵巢癌和子宮內膜癌診斷中的應用.中國衛生檢驗雜志, 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. Hellstr?m 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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