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:10.1038/s41467-024-46994-2

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

Nat Commun. 2024 Mar 29;15(1):2764. doi: 10.1038/s41467-024-46994-2.

Authors

Antonio Agostini^{1

2}, Geny Piro^{3

4}, Frediano Inzani⁵, Giuseppe Quero^{6

7}, Annachiara Esposito^{1

2}, Alessia Caggiano^{1

2}, Lorenzo Priori^{1

2}, Alberto Larghi⁸, Sergio Alfieri^{6

7}, Raffaella Casolino⁹, Giulia Scaglione⁵, Vincenzo Tondolo¹⁰, Giovanni Cammarota^{11

12}, Gianluca Ianiro^{11

12}, Vincenzo Corbo¹³, Andrew V Biankin^{9

14

15}, Giampaolo Tortora^{1

2}, Carmine Carbone^{16

17}

Affiliations

¹ Medical Oncology, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
² Medical Oncology, Department of Translational Medicine, Catholic University of the Sacred Heart, Rome, Italy.
³ Medical Oncology, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. geny.piro@policlinicogemelli.it.
⁴ Medical Oncology, Department of Translational Medicine, Catholic University of the Sacred Heart, Rome, Italy. geny.piro@policlinicogemelli.it.
⁵ Department of Anatomic Pathology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
⁶ Pancreatic Surgery Unit, Gemelli Pancreatic Advanced Research Center (CRMPG), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
⁷ Digestive Surgery Unit, Department of Translational Medicine, Catholic University of the Sacred Heart, Rome, Italy.
⁸ Digestive Endoscopy Unit, Fondazione Policlinico A. Gemelli IRCCS and Center for Endoscopic Research, Therapeutics and Training, Catholic University, Rome, Italy.
⁹ Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK.
¹⁰ General Surgery, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
¹¹ Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
¹² Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy.
¹³ Department of Diagnostics and Public Health, University of Verona, 37134, Verona, Italy.
¹⁴ West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK.
¹⁵ South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, NSW 2170, Australia.
¹⁶ Medical Oncology, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. carmine.carbone@policlinicogemelli.it.
¹⁷ Medical Oncology, Department of Translational Medicine, Catholic University of the Sacred Heart, Rome, Italy. carmine.carbone@policlinicogemelli.it.

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.

MeSH terms

Adenocarcinoma, Mucinous* / genetics
Carcinoma, Pancreatic Ductal* / genetics
Carcinoma, Pancreatic Ductal* / pathology
Homeodomain Proteins / genetics
Humans
Hyperplasia
Pancreatic Intraductal Neoplasms* / genetics
Pancreatic Neoplasms* / diagnosis
Pancreatic Neoplasms* / genetics
Pancreatic Neoplasms* / pathology

Substances

NKX6-2 protein, human
Homeodomain Proteins

Abstract

MeSH terms

Substances

Grants and funding