title: Serum human epididymis protein 4 vs. carbohydrate antigen 125 and their combination for endometrial cancer diagnosis: a meta-analysis.
abstract: Cancer antigen 125 (CA125) and Human epididymis protein 4 (HE4) appear to be promising predictors for endometrial cancer (EC). However, conflicting results exist in the diagnostic performance comparison among CA125 and HE4.
  
  
  
  A systematic review was conducted using PubMed, EMBASE and other databases till December 2015. All studies included were closely assessed with the QUADAS. Diagnostic value of HE4, CA125 and HE4+CA125 was systematically evaluated, and comparison among the predictive performances of HE4, CA125 were conducted. Sensitivity, specificity, DOR (diagnostic odds ratio), and area under the SROC curve were summarized with a random model. Meta-regression was used to explore the heterogeneity.
  
  
  
  8 studies including 1832 cases (1129 in the study group and 703 in the control group) were included in our meta-analysis. Mean estimates of HE4 and their 95% CIs were: sensitivity 0.53 (95% CI: 0.50-0.56), specificity 0.91 (95% CI: 0.89-0.93), DOR 17.01 (95% CI: 7.88-36.72). The area under the SROC curve of HE4 in the diagnosis of EC was 0.77. However, CA125 had lower sensitivity, specificity, DOR, and the area under the SROC in diagnosis of EC with sensitivity 0.26 (95% CI: 0.24-0.29), specificity 0.81 (95% CI: 0.78-0.84), DOR 2.61 (95% CI: 0.92-7.41), and the area under the SROC 0.37. In patients with EC diagnosed by HE4+CA125, the overall sensitivity was 0.58 (95% CI: 0.54-0.62) and a specificity of 0.92 (95% CI: 0.89-0.94) in predicting EC. DOR and the area under the SROC curve of HE4+CA125 for diagnosis of EC were 21.86 (95% CI: 11.08-43.15) and 0.83 respectively, which showed a higher level of diagnostic accuracy than HE4 alone.
  
  
  
  HE4 is helpful for distinguishing EC from healthy and benign disease. CA125 is not better than HE4 either for EC diagnosis. HE4+CA125 is promising a predictor of EC to replace He4, but its utilization requires further exploration.
authors.affiliation: Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Huangpu District, Shanghai, China. xyi@fudan.edu.cn.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: Y-L
authors.initials: YL
authors.lastname: Ren
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.forename: X-F
authors.initials: XF
authors.lastname: Yi
authors.forename: H-Y
authors.initials: HY
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D016889:Endometrial Neoplasms / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D011506:Proteins / Q000378:metabolism*; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human