WAP four-disulfide core domain protein 2 (WFDC2) (WFDC2)

WAP four-disulfide core domain protein 2 (WFDC2), commonly known as Human Epididymis Protein 4 (HE4), is a small secreted glycoprotein primarily recognized as a highly sensitive and specific biomarker for ovarian cancer [1, 6]. Encoded by the WFDC2 gene, it belongs to the whey acidic protein (WAP) family and is thought to function as a protease inhibitor involved in innate immunity and sperm maturation [2, 5]. In oncological contexts, WFDC2 is significantly overexpressed in serous and endometrioid ovarian carcinomas, as well as lung adenocarcinomas, where it promotes tumor progression by activating the AKT signaling pathway and inducing epithelial-mesenchymal transition (EMT) [3, 12]. While currently utilized in clinical practice for monitoring disease recurrence and risk stratification (e.g., the ROMA index), WFDC2 is also an emerging therapeutic target [13, 17]. Experimental strategies, including siRNA-mediated knockdown of WFDC2 mRNA, have demonstrated the ability to inhibit cell migration, invasion, and chemoresistance in preclinical models [12, 24]. Therapeutic development focuses on neutralizing its pro-metastatic activity and modulating the immunosuppressive tumor microenvironment it helps maintain [10, 18].

Other names

HE4Human epididymis protein 4WAP5EDDM4Epididymal secretory protein E4Major epididymis-specific protein E4Putative protease inhibitor WAP5

Gene silencing (mRNA knockdown) or protein inhibition to suppress tumor metastasis and chemoresistance