Proteomics of pediatric adrenocortical tumors

ABSTRACT: Pediatric adrenocortical tumors (pACT) are biologically heterogeneous and incompletely classified by histopathology. To elucidate proteome-level tumor organization, we performed mass spectrometry–based proteomic profiling of 83 pACT and 43 normal adrenal samples. Unsupervised clustering identified four distinct molecular subtypes partially overlapping with histological diagnoses. These subtypes reflected discrete biological states: stromal–immune enrichment with reduced steroidogenesis, mitochondrial and steroidogenic activation, IGF/mTOR-driven anabolic reprogramming, and highly proliferative chromatin-remodeled carcinoma states. Proteomic clusters correlated strongly with endocrine phenotype, proliferative index, vascular invasion, and survival, outperforming conventional pathology. A five-protein classifier (DAAM2, CIP2A, TSC2, PALS2, P3H1) reproduced subtype structure with 92.8% cross-validated accuracy. Cluster-specific analysis therapeutic vulnerabilities, including IGF-axis activation and epigenetic and DNA replication targets in aggressive tumors. These data establish a proteome-based classification of pACT integrating metabolic, proliferative, immune features, providing a framework for molecularly guided risk assessment and precision therapy in this rare cancer.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Adrenal Gland

DISEASE(S): Adrenocortical Carcinoma

SUBMITTER: Andreas Metousis  

LAB HEAD: Matthias Mann

PROVIDER: PXD080313 | Pride | 2026-10-26

REPOSITORIES: Pride