Diagnostic Value of Human Epididymis Protein 4 Compared with Mesothelin for Ovarian Cancer: a Systematic Review and Meta-analysis

Background and Purpose: Ovarian cancer is the leading cause of death among gynecologic cancers because ofthe lack of effective early detection methods. Accuracies of the human epididymis protein 4 (HE4) and mesothelinin detecting ovarian cancer have never been systematically assessed. The current systematic review aimed to tacklethis issue.
Methods: MEDLINE, EMBASE, and Cochrane databases were searched (September 1995–November2011) for studies on the diagnostic performances of HE4 and mesothelin in differentiating ovarian cancer fromother benign gynecologic diseases. QUADAS items were used to evaluate the qualities of the studies. Meta-DiScsoftware was used to handle data from the included studies and to examine heterogeneity. All included studiesfor diagnostic performance were combined with sensitivity, specificity, positive likelihood ratio (PLR), negativelikelihood ratio (NLR), diagnostic odds ratios (DORs) with 95% confidence intervals (CIs), summary receiveroperating characteristic (SROC) curves, and areas under the SROC curves (AUC).
Results: A total of 18 studiesand 3,865 patients were eligible for the final analysis. The pooled sensitivity estimates for HE4 (74.4%) weresignificantly higher than those for mesothelin (49.3%). The pooled specificity estimates for mesothelin (94.5%)were higher than those for HE4 (85.8%). The pooled DOR estimates for HE4 (26.22) were higher than those formesothelin (24.01). The SROC curve for HE4 showed better diagnostic accuracy than that for mesothelin. ThePLR and NLR of HE4 were 6.33 (95% CI: 3.58 to 11.18) and 0.27 (95% CI: 0.21 to 0.34), respectively. The PLRand NLR for mesothelin were 11.0 (95% CI: 6.21 to 19.59) and 0.51 (95% CI: 0.42 to 0.62), respectively. Thecombination of the two tumor markers or their combination with CA-125 increased sensitivity and specificityto different extents.
Conclusion: The diagnostic accuracy of HE4 in differentiating ovarian cancer from otherbenign gynecologic diseases is better than that of soluble mesothelin-related protein. Combinations of two ormore tumor markers show more sensitivity and specificity.