Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms
Year: 2021
Type: article
Study design: Observational Study
Abstract: Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous. Here, we use a multi-omics approach to uncover the molecular factors underlying this heterogeneity. Transcriptomic analysis of 84 PNEN specimens, drawn from two cohorts, is substantiated with proteomic profiling and identifies four subgroups: Proliferative, PDX1-high, Alpha cell-like and Stromal/Mesenchymal. The Proliferative subgroup, consisting of both well- and poorly differentiated specimens, is associated with inferior overall survival probability. The PDX1-high and Alpha cell-like subgroups partially resemble previously described subtypes, and we further uncover distinctive metabolism-related features in the Alpha cell-like subgroup. The Stromal/Mesenchymal subgroup exhibits molecular characteristics of YAP1/WWTR1(TAZ) activation suggestive of Hippo signaling pathway involvement in PNENs. Whole-exome sequencing reveals subgroup-enriched mutational differences, supported by activity inference analysis, and identifies hypermorphic proto-oncogene variants in 14.3% of sequenced PNENs. Our study reveals differences in cellular signaling axes that provide potential directions for PNEN patient stratification and treatment strategies.
Source: Cell Reports
Authors: Kevin C. Yang, Steve E. Kalloger, John J. Aird, Michael K.C. Lee, Christopher Rushton, Karen L. Mungall, Andrew J. Mungall, Dongxia Gao, Christine Chow, Jing Xu, Joanna M. Karasinska, Shane Colborne, Steven J.M. Jones, Jörg Schrader, Ryan D. Morin, Jonathan M. Loree, Marco A. Marra, Daniel J. Renouf, Gregg B. Morin, David F. Schaeffer, Sharon M. Gorski
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Award: G4731309827
OpenAlex ID: W3206160743