Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms

doi:10.1016/j.celrep.2021.109817

Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms

2021-10-01

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DOI：10.1016/j.celrep.2021.109817

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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 protooncogene 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.

Keywords:

SOMATIC MUTATIONS

SIGNALING PATHWAY

CELL

TUMORS

EXPRESSION

GENE

YAP

TAZ

BIOCONDUCTOR

GUIDELINES

Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms

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