Acinar cell carcinoma (ACC) and pancreatoblastoma (PBL) are rare pancreatic malignancies of acinar differentiation. We conducted proteogenomic profiling of patient tumor cohorts with comparison to pancreatic ductal adenocarcinoma (PDAC) and benign tissue.
The proteome depicts ACC and PBL as similar but separate entities and distinct from PDAC. ACC and PBL are enriched with proteins involved in RNA processing and transport, chromosome organization, and the mitoribosome, whereas PDACs overexpress proteins related to actin-based processes, extracellular matrix, and immune-active stroma. We examined pathway differences in metabolic adaptation, epithelial to mesenchymal transition, and DNA repair.
We discovered proteomic changes in both Wnt-CTNNB1 and -IGF2 pathways. We identified 17 ACC-specific markers that highlight ACC as a metabolic disease with mitochondrial dysfunction and 34 PBL-specific proteins that mark this pediatric cancer with an embryonic stem cell phenotype and changes in chromosomal proteins and the cell cycle.
This study offers a first proteomic view of two poorly understood pancreatic neoplasms and provides new pathway and protein targets for future diagnostic and therapeutic development.