CSIG-29. CLINICAL AND TRANSCRIPTOMIC DATASET IDENTIFIES LARGE CHANGES IN IMMUNE AND HORMONAL SIGNALING AMONGST RECURRENT PATIENTS WITH CRANIOPHARYNGIOMA

Abstract

Abstract INTRODUCTION Craniopharyngioma is a low-grade suprasellar brain tumor that often produces deficiencies of pituitary hormones, including growth hormone. Although epidemiological data are reassuring that growth hormone does not lead to craniopharyngioma recurrence, the theoretical risk is cause for concern. To address this and other questions related to the care of individuals with recurrent craniopharyngioma, we analyzed gene expression in craniopharyngiomas in the context of clinical data. We envision insights that could guide decisions about hormone replacement and tumor-focused treatment alternatives. METHODS Clinical information was abstracted for a cohort of individuals diagnosed with craniopharyngioma at the Children’s Hospital of Philadelphia between 2016 - 2020. In parallel, tumor transcriptomic data for patients with craniopharyngioma were collected from the Children’s Brain Tumor Network (CBTN) and matched to clinical data where applicable. Bulk RNA-sequencing analysis, pathway analysis, and immune deconvolution (xCell) of samples was performed in R to identify transcript-level changes that distinguish recurrent from initial craniopharyngioma. RESULTS CBTN data was available for 54 initial tumor samples and 17 recurrent tumor samples, with matched clinical data available for 33 samples (26 initial, 7 recurrent). We did not find differences in clinical characteristics between individuals with versus without recurrence. Pathway analysis notably suggested altered levels of antigen presentation (NES: 2.97), Programmed cell death (NES: 2.34), WNT signaling (NES: 1.97), and Growth Hormone Signaling (NES: -1.277) amongst recurrent samples when compared against initial samples. Deconvolution of samples showed altered levels of M2-like macrophages (39.2% increased) and CD4+ T-helper-2 cells (-54.7% decreased) in recurrent samples compared against initial samples. Preliminary work is being completed to frame these results in the context of available clinical neuroendocrine data. CONCLUSION This work highlights marked changes in immune and hormonal signaling in samples from recurrent craniopharyngioma tumors. These insights have potential therapeutic implications that deserve further investigation.