A study led by ALIPANC researchers from the Maimonides Biomedical Research Institute of Cordoba (IMIBIC) and the University of Córdoba (UCO) has provided the first comprehensive RNA spliceosomic landscape of pancreatic neuroendocrine tumors (PanNETs). The results, published in Endocrine Pathology, show through integrative transcriptomic analysis of 174 tumor samples that PanNETs can be classified into three robust spliceosomic subgroups (SPN1, SPN2, and SPN3) with distinct clinical, molecular, and biological behavior.

The study reveals an unprecedented discovery in these tumors: a direct association between the expression profile of the splicing machinery and its functional product, the alternative splicing variants. Specifically, SPN1 exhibits intermediate clinical behavior alongside enhanced mTOR signaling; SPN2 is characterized by a less secretory phenotype, enriched alpha-cell markers and somatostatin receptors (SSTR), higher metastasis, and frequent mutations in MEN1 and DAXX/ATRX; while SPN3 comprises mainly low-grade tumors with beta-cell markers, the lowest mutational rate, and all highly proliferative neoplasms.

Furthermore, the results demonstrate that alterations in specific splicing factor families condition distinct RNA splicing events that affect key signaling, metabolic, and regulatory pathways. This integrative approach deepens the understanding of PanNET molecular heterogeneity and establishes RNA splicing profiling as a promising foundation for discovering novel biomarkers and developing personalized therapeutic strategies.

Reference article:

Ricardo Blázquez-Encinas, Víctor García-Vioque, Andrea Mafficini, Luca Landoni, Daniel Ruiz-Palacios, Laura Gutiérrez-Camacho, María Trinidad Moreno-Montilla, Nicolás Alcalá, Sebastián Ventura, Eduardo Eyras, Salvatore Paiella, Roberto Salvia, Vita Rovite, Matthieu Foll, Claudio Luchini, Lynnette Fernandez-Cuesta, Rita T. Lawlor, Aldo Scarpa, Alejandro Ibáñez-Costa, Sergio Pedraza-Arevalo, Justo P. Castaño. An Integrative RNA Spliceosomic Landscape of Pancreatic Neuroendocrine Tumors Identifies Clinically Relevant Molecular Subgroups. Endocrine Pathology 2026; 37:28. https://doi.org/10.1007/s12022-026-09923-1