Bioconjugation Methods for Improving the Efficiency of Human Epididymis Protein 4 (HE4) Biomarker for Detecting Ovarian Cancer at Early Stages

Abstract

Ovarian cancer (OC), whose incidence increases with age, is one of the most commoncancer types in woman. OC can be successfully treated if detected early but the diagnosis ofOC at early stages is difficult since there are no obvious symptoms and no screening testhas proven to be effective. Human Epididymis Protein 4 (HE4) is a serum marker recentlydeveloped for earlier detection of ovarian carcinoma. HE4 belongs to the family of WheyAcidic four-disulfide core (WFDC) proteins (WAP). This glycoprotein (gene nameWFDC2) is highly expressed by ovarian carcinomas, leading to its potential application as aserum biomarker for this cancer. Since the efficiency and sensitivity of HE4 biomarker isstill insufficient for early diagnosis of OC, we attempt to develop improved biosensordetection strategies based on bioconjugation with nanobodies against HE4. Several approaches,by which the introduction of a site-specific and bio-orthogonal functional group can pave theway to a uniform orientation of the HE4 nanobodies at the biosensor surface, will be explored.This should lead to an improved sensitivity since all nanobodies will have their active regionsaccessible for binding the biomarker.