Spatial Analysis of IPMNs Defines a Paradoxical KRT17-Positive, Low-Grade Epithelial Population Harboring Malignant Features

Intraductal papillary mucinous neoplasms (IPMNs) represent one of the few radiologically identifiable precursors to pancreatic ductal adenocarcinoma (PDAC); however, identifying lesions at greater risk of progressing to malignancy remains elusive. To investigate the transcriptional changes that occur during IPMN progression, we performed spatial transcriptomics and single-cell RNA sequencing on IPMN specimens. We identified a subpopulation of histologically low-grade IPMN epithelial cells that express malignant transcriptional features including KRT17, S100A10 and CEACAM5, markers that are enriched in PDAC. Our study demonstrates that KRT17 marks a distinct signature in a subpopulation of epithelial cells within histologically low-grade IPMN which may represent a higher risk of progression to carcinoma.

We utilized PDAC sequencing data from the dbGaP accession number phs002071, and healthy pancreas sequencing data from Gene Expression Omnibus Series GSE229413. In addition to that, we included sequencing from 2 new specimens which are deposited to this submission, consisting of 1 main duct IPMN and 1 side branch IPMN. FASTQ files of these sequencing runs are available through this dbGaP submission.

• Study Design:
  • Collection
• Study Type:
  • Observational
• Total number of consented subjects: 2
• Subject Sample Telemetry Report (SSTR)

• PubMed

All human subjects research was conducted in accordance with approval by the Institutional Review Board at the University of Michigan (IRB HUM00025339). Medical chart review was used to screen for potential study patients with pancreatic cysts at the University of Michigan.

• Primary Phenotype: Pancreatic Intraductal Neoplasms
• Spatial Transcriptomics
• Single Cell Analysis
• Pancreatic Cyst

• KRT17
• TFF2
• CEACAM5
• S100A10

• Principal Investigator
  • Eileen S. Carpenter, MD, PhD. University of Michigan, Ann Arbor, MI, USA.
• Funding Sources
  • IK2BX005875. Department of Veterans Affairs, Ann Arbor, MI, USA.
  • Cancer Discovery Award. Rogel Cancer Center, Ann Arbor, MI, USA.
  • Career Development Award. American College of Gastroenterology, Bethesda, MD, USA.
• Sequencing Center
  • Advanced Genomics Core. University of Michigan, Ann Arbor, MI, USA.