WFDC2 – Ovarian Carcinoma

Two independent multi‑patient studies have investigated the performance of HE4—a protein encoded by WFDC2—as a serum biomarker in the context of ovarian carcinoma. In one study, HE4, used in combination with CA125, was evaluated in a screening trial among women at elevated risk, which yielded a surgical positive predictive value (PPV) above 25% (PMID:24789859). In a second study, the prognostic effectiveness of HE4 was examined in epithelial ovarian cancer patients, including those harboring BRCA mutations. This study, involving over 400 patients, reported that normalization of HE4 levels correlated with high specificity and suggested that HE4 alone might effectively predict 1‑year recurrence‑free survival (PMID:38670560).

Although these studies provide compelling clinical data supporting the utility of HE4 for risk stratification and management in ovarian carcinoma, there is no evidence linking specific WFDC2 germline variants to disease causation. Consequently, while the association is clinically significant as a diagnostic and prognostic biomarker, the genetic evidence remains limited. Functional investigations similarly offer only limited mechanistic insights into how alterations in HE4 expression might contribute directly to tumorigenesis.

References

• Cancer epidemiology, biomarkers & prevention • 2014 • Use of CA125 and HE4 serum markers to predict ovarian cancer in elevated-risk women PMID:24789859
• Journal of gynecologic oncology • 2024 • The effectiveness of CA125 and HE4 as clinical prognostic markers in epithelial ovarian cancer patients with BRCA mutation PMID:38670560

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