Identification of spatially-resolved markers of malignant transformation in Intraductal Papillary Mucinous Neoplasms

Antonio Agostini, Geny Piro (), Frediano Inzani, Giuseppe Quero, Annachiara Esposito, Alessia Caggiano, Lorenzo Priori, Alberto Larghi, Sergio Alfieri, Raffaella Casolino, Giulia Scaglione, Vincenzo Tondolo, Giovanni Cammarota, Gianluca Ianiro, Vincenzo Corbo, Andrew V. Biankin, Giampaolo Tortora and Carmine Carbone ()
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Antonio Agostini: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Geny Piro: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Frediano Inzani: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Giuseppe Quero: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Annachiara Esposito: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Alessia Caggiano: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Lorenzo Priori: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Alberto Larghi: Catholic University
Sergio Alfieri: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Raffaella Casolino: University of Glasgow, Garscube Estate
Giulia Scaglione: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Vincenzo Tondolo: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Giovanni Cammarota: Università Cattolica del Sacro Cuore
Gianluca Ianiro: Università Cattolica del Sacro Cuore
Vincenzo Corbo: University of Verona
Andrew V. Biankin: University of Glasgow, Garscube Estate
Giampaolo Tortora: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Carmine Carbone: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract The existing Intraductal Papillary Mucinous Neoplasm (IPMN) risk stratification relies on clinical and histological factors, resulting in inaccuracies and leading to suboptimal treatment. This is due to the lack of appropriate molecular markers that can guide patients toward the best therapeutic options. Here, we assess and confirm subtype-specific markers for IPMN across two independent cohorts of patients using two Spatial Transcriptomics (ST) technologies. Specifically, we identify HOXB3 and ZNF117 as markers for Low-Grade Dysplasia, SPDEF and gastric neck cell markers in borderline cases, and NKX6-2 and gastric isthmus cell markers in High-Grade-Dysplasia Gastric IPMN, highlighting the role of TNFα and MYC activation in IPMN progression and the role of NKX6-2 in the specific Gastric IPMN progression. In conclusion, our work provides a step forward in understanding the gene expression landscapes of IPMN and the critical transcriptional networks related to PDAC progression.

Date: 2024
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DOI: 10.1038/s41467-024-46994-2

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