TMET-37. SODIUM-DEPENDENT GLUCOSE TRANSPORTER 2 (SGLT2) IS OVEREXPRESSED IN THE MAJORITY OF ATRTS AND A SUBSET OF PEDIATRIC PATIENTS WITH HIGH-GRADE GLIOMA; A POTENTIAL IMAGING AND THERAPEUTIC TARGET

Abstract

Abstract Sodium glucose cotransporters (SGLT) are a class of glucose transporters independent of the conventional glucose transporters (GLUT). Like the GLUT, SGLT2 plays an important role in glucose uptake in many solid cancers. Importantly, SGLT2 inhibitors are a new class of anti-diabetic drugs and have recently been investigated as a potential anti-cancer therapy in a variety of solid cancers. In fact, a recent study in adult high-grade gliomas showed that an SGLT-specific PET imaging probe ([18F] Me-4FDG) is sensitive for visualization of high-grade glioma (HGG) with superior tumor-normal brain uptake relative to 18F-FDG-PET. We aimed to investigate the expression of SGLT2 within pediatric brain tumor subtypes using RNA sequencing data from PedcBioPortal and immunohistochemistry of tissue microarrays (TMAs). Using the RNA sequencing data from 603 patients with pediatric brain tumors, we found that HGGs have the highest SGLT2 expression (Z score=0.13± 1.03) and were significantly higher compared to low-grade gliomas (Z score= -0.12, p=0.049), medulloblastomas (Z score=-0.28, p=0.001), and ependymomas (Z score=-0.30, p=0.002). Atypical teratoid rhabdoid tumors (ATRT) also had significantly higher Z score (0.10±0.67) compared to medulloblastomas (p=0.038), and ependymomas (p=0.049). There was no significant difference between HGGs and ATRTs in SGLT2 expression (p=0.899). Analysis of 4 TMAs including HGGs, medulloblastomas, ependymomas, and ATRTs after SGLT2 immunohistochemistry demonstrated strong membranous staining in a small subset and moderate-weak staining in the majority of HGGs. The majority of ATRTs were positive. The majority of medulloblastomas and ependymomas were negative, noting that the membranous nature of the staining may be a limiting factor in evaluation of tumors with less cytoplasm. In conclusion, our work demonstrates that SGLT2 has heterogeneous expression in pediatric brain tumors and is overexpressed in the majority of ATRTs, and a subset of pediatric HGGs, and may represent a compelling paradigm that integrates metabolic imaging and therapy of these tumors.