P10.09.B SERPINB1 IMPROVES CLINICAL OUTCOME THROUGH INCREASING APOPTOSIS AND CHEMOSENSITIVITY IN MEDULLOBLASTOMA

Abstract BACKGROUND Medulloblastoma (MB) is one of the most prevalent pediatric brain malignancies and makes up ~20% of all primary brain tumors in children. Current treatment options are not curative for approximately 30% of patients and leave survivors with an impaired quality of life. Elevated expression of SERPINB1 is associated with increased patient survival, but the mechanism responsible for this benefit has not been defined. The aim of this study was to determine the clinical relevance of SERPINB1 in MB by identifying its role on apoptosis and chemosensitivity. MATERIAL AND METHODS We utilized single cell and single nuclei sequencing datasets of primary MB tumors, established Group 3 MB cell lines, and primary patient-derived MB tissue of all subtypes to study SERPINB1. Clinically relevant chemotherapies used were camptothecin, etoposide, and cisplatin. RESULTS We identified the expression of SERPINB1 mRNA and protein in primary MB tissue, which was not associated with molecular and histological subtype. In our tissue cohort (n=41), we found that SERPINB1 tumor positivity, but not staining intensity, protected MB patients and increased 10-year overall (p=0.008) and relapse-free survival (p=0.007). Mechanistically, recombinant SERPINB1 overexpression in MB cells did not impact anoikis resistance but impaired cell adhesion and enhanced early and late apoptosis as well as sensitivity to several chemotherapeutics (up to 10-fold) in vitro. CONCLUSION These data suggest that SERPINB1 improves clinical outcome via enhancing apoptosis and chemosensitivity in MB patients. This knowledge can be used to readjust chemotherapeutic regimens in this vulnerable patient group to limit toxicity.