Pilot Study: Exploring PCSK9 in Maternal Serum as Potential Noninvasive Biomarker for Neural Tube Defects

Abstract

Objectives: Neural tube defects (NTDs) are caused by inadequate closing of the neural tube. Alpha-fetoprotein has limitations due to its poor sensitivity and specificity in NTD detection. Proprotein convertase subtilisin/kexin type 9 (PCSK9) appears to have an escalating role in neurogenesis. This study aimed to evaluate the two forms of PCSK9 (Mature PCSK9 and furin cleaved) circulating in NTD maternal sera as a potential novel non-invasive biochemical marker for prenatal screening of NTDs. Materials and Methods: In this case-control study, the presence of PCSK9 in serum samples of 30 pregnant women with current NTD fetuses (case group) and 30 pregnant women with a healthy singleton pregnancy (control group) was evaluated by Western blot analysis followed by the immuno-precipitation approach. Results: Median of mature PCSK9/furin ratio among the case group was 0.92 (0.05-2.54) versus 1.29 (0.19-6.62) among the control group (P = 0.02). Receiver operating characteristic curve analysis for mature PCSK9/furin ratio displayed a sensitivity and specificity equal to 63.3%. Conclusions: The ratio of mature PCSK9 to furin cleaved form was significantly reduced among women with current NTD fetuses compared to women having healthy pregnancies. This ratio can be a potential original biochemical marker in the non-invasive prenatal screening of NTDs.