Neuroendocrinology and Pituitary

SUN-082 - Proteomic and Metabolomic Profiling in Craniopharyngioma

Sunday, June 14, 2026

9:00 AM - 4:00 PM CT

Late-Breaking Poster Presenter(s)

Odelia Cooper, MD

Professor of Medicine
Cedars Sinai Medical Center
Los Angeles, CA, United States

Co-Author(s)

AB

Anat Ben-Shlomo, MD (she/her/hers)

Staff physician
Cedars-Sinai Health Sciences University
Los Angeles, California, United States
AL

Artak Labadzhyan, MD

Cedars Sinai Medical Center
LOS ANGELES, California, United States
NL

Ning-Ai Liu, MD, PhD

Cedars Sinai Medical Center
LOS ANGELES, California, United States

Senior Author/Primary Investigator(s)

AM

Adam N. Mamelak, MD

Professor of Neurosurgery
Cedars Sinai Medical Center
Los Angeles, California, United States

Disclosure(s):

Odelia Cooper, MD: Camurus: Advisory Board (); Rhythm Pharmaceuticals: Honorarium Recipient ()

Background: Craniopharyngiomas (CP) are rare, benign parasellar tumors that predispose patients to hypothalamic obesity, type 2 diabetes mellitus (T2DM), hyperlipidemia, and other metabolic dysfunctions. Studies suggest proteins associated with fatty acid metabolic processes, inflammatory response, and neuron development may be associated with CP pathogenesis, subtype, and recurrence. Yet associations with metabolic complications in CP are relatively unexplored. This study assessed differential expression of circulating and tumoral proteins and metabolites in CP and their association with metabolic outcomes.

Methods: We collected plasma from patients with pathology-confirmed CP for proteomic and metabolomic analysis on mass spectrometry; proteomic analysis was performed on banked tumor tissue. Group differences in tumor tissue protein expression, plasma protein levels, and metabolite profiles were assessed using two-sample t-tests. Univariate logistic regression was conducted to evaluate associations with clinical outcomes. P-values were corrected for multiple comparisons using the Benjamini-Hochberg false discovery rate (FDR) method; only significant results (FDR < 0.05) were reported unless otherwise noted.

Results: Ten patients were enrolled. Mean age at assessment was 40.7 years (SD 13.4); mean duration from surgery was 8.4 years (SD 5.8). 80% had adamantinomatous (aCP) and 20% papillary CP (pCP); 80% had adult-onset (AoCP), and 20% childhood-onset CP (CoCP). Tumor proteomics showed alterations in genes associated with metabolic function, including upregulation of NAGK (FDR 0.09) and TBB6 (FDR 0.09) in those with and without T2DM and ARLY in those using GLP-1RA. Patients with hyperlipidemia showed downregulated immune and inflammatory pathway plasma metabolites 9-HODE and inosine. 21 proteins downregulated in aCP tissue and 1 in plasma were related to neurocognition (MMP2, NGF), motor function (KIF1A), neuroendocrine secretory function (STX1a), hypothalamic signaling pathways (SYT5), and neurodevelopment (AP1G1). These findings are consistent with increased endocrine symptoms seen with aCP presentation compared with more neurologic and hypothalamic symptoms in pCP. Patients with AoCP showed downregulated tumoral and plasma proteins involved in adipose and hepatic metabolism (GPDA) and neurodevelopment (HPPD) as well as downregulated tumor PRRC2A, associated with severe obesity, and IFI30, associated with T2DM. These findings are consistent with the more substantial metabolic disease that tends to develop in CoCP.

Conclusion: Differential expression of tumoral and plasma proteins in metabolic, neurologic, and hypothalamic pathways correspond to the observed clinical differences between CP subtypes and childhood vs adult onset. Our preliminary results suggest a need to develop a more age- and subtype-dependent approach CP management.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*