Abstract
Solid pseudopapillary neoplasm (SPN) is a rare neoplasm of the pancreas of unclear histogenesis. The biology of SPN remains poorly understood, especially at proteome level. We report the first comprehensive integrated proteogenomic characterization of SPN and investigate differences to other pancreatic neoplasms.We collected patient samples from SPNs, pancreatic ductal adenocarcinomas, acinar cell carcinomas, pancreatoblastomas, well-differentiated pancreatic neuroendocrine tumors, and benign exocrine pancreatic tissues. Samples were exome-sequenced and proteomes characterized by LC-MS. Metascape was used to conduct pathway enrichment analyses. Gene Set Enrichment Analysis was performed by projecting protein expression onto GO, Hallmark, KEGG, and Reactome pathway sets. We calculated immune scores from the protein expression matrix of all samples. We inferred immune cell abundance using the xCell tool.
We discovered that the SPN proteome is clearly distinct from that of other pancreatic entities, and that lysosome-related proteins were enriched in SPN, suggesting a possible link to metabolic adaptation mechanisms in low-nutrient environments since lysosomal degradation products are biological energy sources.
We also discovered that MITF, one of lysosomal process regulators, was highly specific for SPN and superior to TFE3. Furthermore, our proteome analysis found that SPN was an immune-cold tumor with low MHC class I molecule expression compared to pancreatic ductal adenocarcinoma. To expand possible treatment options for SPN, we identified 21 protein targets that could be targeted with already approved drugs.
We present the first proteogenomic characterization of SPN. Our results contribute to a deeper understanding of the biology of SPN and the distinction of SPN from other pancreatic neoplasms such as PDAC, ACC, PBL, or PNET. Our discoveries of new SPN-specific protein biomarkers have direct implications for the development of novel therapeutic targets.