Diagnostic value of serum human epididymis protein 4, carbohydrate antigen 125 and their combination in endometrial cancer: A meta-analysis

Medicine (Baltimore). 2023 Aug 18;102(33):e34737. doi: 10.1097/MD.0000000000034737.

Abstract

Background: To systematically analyze the value of human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) in the diagnosis of endometrial cancer, so as to provide evidence-based medical evidence for the selection of serum tumor markers in the early screening of endometrial cancer.

Methods: We comprehensively searched relevant literature in the Cochrane Library, EMBASE, PubMed, Web of Science, CNKI, VIP, WanFang, and CBM from the date of establishment to November 31, 2021. Quality assessment of diagnostic accuracy studies 2 was applied to evaluate the quality of the included literature. We used Stata 16.0 to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) and plot summary receiver operating characteristic curve, as well as to assess diagnostic accuracy using the area under the curve (AUC).

Results: A total of 25 studies, including 1980 patients and 2345 controls, were included in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 were 0.58 (95% CI 0.52-0.63), 0.95 (95% CI 0.92-0.97), 11.57 (95% CI 6.88-19.48), 0.45 (95% CI 0.39-0.51), 25.92 (95% CI 14.84-45.26), and 0.80 (95% CI 0.76-0.83), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of CA125 were 0.41 (95% CI 0.34-0.49), 0.91 (95% CI 0.85-0.95), 4.55 (95% CI 2.73-7.58), 0.65 (95% CI 0.57-0.74), 7.03 (95% CI 3.92-12.62), and 0.68 (95% CI 0.64-0.72), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 + CA125 were 0.67 (95% CI 0.60-0.73), 0.92 (95% CI 0.87-0.95), 8.59 (95% CI 5.32-13.86), 0.36 (95% CI 0.30-0.44), 23.80 (95% CI 13.86-40.86), and 0.85 (95% CI 0.82-0.88), respectively.

Conclusion: This Meta-analysis found that HE4 alone or in combination with CA125 showed better diagnostic efficacy than CA125, regardless of clinical stage and pathological type. HE4 + CA125 had slightly higher diagnostic efficiency than HE4, but did not show significant advantages. While the studies were heterogeneous, the credibility of the findings needs to be further confirmed by more homogeneous, prospective, and large sample size studies.

Publication types

  • Meta-Analysis

MeSH terms

  • Area Under Curve
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Carbohydrates
  • Endometrial Neoplasms* / diagnosis
  • Female
  • Humans
  • Prospective Studies

Substances

  • Biomarkers, Tumor
  • CA-125 Antigen
  • Carbohydrates
  • WFDC2 protein, human
  • MUC16 protein, human