Nature Communications (Mar 2024)

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,
  • Carmine Carbone

DOI
https://doi.org/10.1038/s41467-024-46994-2
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 16

Abstract

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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.