Cell division cycle 42 binding protein beta as a plasma-based biomarker for cerebral cavernous malformations

OBJECTIVE Cerebral cavernous malformations (CCMs) are groups of blood vessels that develop abnormally in both the brain and/or spinal cord. Currently, MRI and/or CT are the primary methods for assessing CCMs. Plasma-based biomarkers could serve as a complement to standard imaging techniques by providing a quantitative and molecular-based technique to detect disease at lower cost. Therefore, the authors evaluated cell division cycle 42 binding protein beta (CDC42BPB) as a potential novel plasma biomarker for CCMs. METHODS Plasma samples were obtained from patients with pathological analysis–confirmed CCM (n = 10, age 1–16 years) and compared to controls (n = 24, age 1–19 years). The protein levels were measured using the Olink Proximity Extension Assay. Findings were confirmed with ELISA. CDC42BPB expression was further analyzed with Western blot and immunohistochemistry analysis in patient-derived primary cells and CCM tissues, respectively. RESULTS CCM patients exhibited significantly higher CDC42BPB plasma levels compared to controls (approximately 6-fold greater expression, p = 0.004). Furthermore, the high CDC42BPB plasma expression was concordant with the protein levels in CCM tissues and patient-derived primary cells. CONCLUSIONS The authors present data supporting the measurement of CDC42BPB plasma level as a putative biomarker for CCMs. These findings have implications relevant to improving diagnosis, follow-up, and molecular pathophysiological analysis.