Spatial analysis of IPMNs defines a paradoxical KRT17-positive, low-grade epithelial population harboring malignant features Article Swipe
Jay Li
,
Justin Macchia
,
Ahmed M. Elhossiny
,
Nandini Arya
,
Padma Kadiyala
,
Georgina L Branch
,
Nicole Peterson
,
Jianhua Liu
,
Richard S. Kwon
,
Jorge D. Machicado
,
Erik‐Jan Wamsteker
,
Allison R. Schulman
,
George Philips
,
Stacy B. Menees
,
Aatur D. Singhi
,
Vaibhav Sahai
,
Jiayun M. Fang
,
Timothy L. Frankel
,
Filip Bednar
,
Marina Pasca di Magliano
,
Jiaqi Shi
,
Eileen S. Carpenter
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.03.18.643943
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.03.18.643943
Background & Aims Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that represent one of the few radiologically identifiable precursors to pancreatic ductal adenocarcinoma (PDAC). Though the IPMN-bearing patient population represents a unique opportunity for early detection and interception, current guidelines provide insufficient accuracy in determining which patients should undergo resection versus surveillance, resulting in a sizable fraction of resected IPMNs only harboring low-grade dysplasia, suggesting that there may be overtreatment of this clinical entity. Methods To investigate the transcriptional changes that occur during IPMN progression, we performed spatial transcriptomics using the Nanostring GeoMx on patient samples containing the entire spectrum of IPMN disease including low-grade dysplasia, high-grade dysplasia, and IPMN-derived carcinoma. Single cell RNA sequencing was performed on side branch and main duct IPMN biospecimens. Results 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. We validated this high-risk gene signature in both single-cell RNA sequenced samples and an external ST dataset containing a larger number of IPMN samples including non-tumor bearing IPMN (i.e. low-grade IPMN in isolation). Immunofluorescence staining of a large cohort of patient tissues confirmed the presence of KRT17-positive cells, which were found to comprise a small subset of epithelial cells within histologically low-grade IPMN in a patchy distribution. Conclusions Our study demonstrates that KRT17 marks a distinct transcriptional signature in a subpopulation of epithelial cells within histologically low-grade IPMN. This population of cells likely represents a transitional state of histologically low-grade epithelial cells undergoing progression to a higher grade of dysplasia and thus may represent a higher risk of progression to carcinoma. Abstract Figure Graphical Abstract
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.03.18.643943
- https://www.biorxiv.org/content/biorxiv/early/2025/03/19/2025.03.18.643943.full.pdf
- OA Status
- green
- References
- 54
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4408604308
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4408604308Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2025.03.18.643943Digital Object Identifier
- Title
-
Spatial analysis of IPMNs defines a paradoxical KRT17-positive, low-grade epithelial population harboring malignant featuresWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-03-19Full publication date if available
- Authors
-
Jay Li, Justin Macchia, Ahmed M. Elhossiny, Nandini Arya, Padma Kadiyala, Georgina L Branch, Nicole Peterson, Jianhua Liu, Richard S. Kwon, Jorge D. Machicado, Erik‐Jan Wamsteker, Allison R. Schulman, George Philips, Stacy B. Menees, Aatur D. Singhi, Vaibhav Sahai, Jiayun M. Fang, Timothy L. Frankel, Filip Bednar, Marina Pasca di Magliano, Jiaqi Shi, Eileen S. CarpenterList of authors in order
- Landing page
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https://doi.org/10.1101/2025.03.18.643943Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2025/03/19/2025.03.18.643943.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2025/03/19/2025.03.18.643943.full.pdfDirect OA link when available
- Concepts
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Population, Medicine, Dysplasia, Pathology, Intraductal papillary mucinous neoplasm, Cancer research, Gastroenterology, Internal medicine, Pancreas, Environmental healthTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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54Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.clinical | 74 |
| abstract_inverted_index.comprise | 208 |
| abstract_inverted_index.distinct | 231 |
| abstract_inverted_index.enriched | 153 |
| abstract_inverted_index.external | 170 |
| abstract_inverted_index.features | 142 |
| abstract_inverted_index.fraction | 58 |
| abstract_inverted_index.mucinous | 6 |
| abstract_inverted_index.patients | 48 |
| abstract_inverted_index.presence | 200 |
| abstract_inverted_index.resected | 60 |
| abstract_inverted_index.spectrum | 101 |
| abstract_inverted_index.staining | 190 |
| abstract_inverted_index.Graphical | 279 |
| abstract_inverted_index.confirmed | 198 |
| abstract_inverted_index.detection | 37 |
| abstract_inverted_index.dysplasia | 265 |
| abstract_inverted_index.harboring | 63 |
| abstract_inverted_index.high-risk | 159 |
| abstract_inverted_index.including | 105, 143, 180 |
| abstract_inverted_index.low-grade | 64, 106, 134, 185, 217, 242, 255 |
| abstract_inverted_index.malignant | 140 |
| abstract_inverted_index.neoplasms | 7 |
| abstract_inverted_index.non-tumor | 181 |
| abstract_inverted_index.papillary | 5 |
| abstract_inverted_index.performed | 88, 118 |
| abstract_inverted_index.represent | 13, 269 |
| abstract_inverted_index.resection | 51 |
| abstract_inverted_index.resulting | 54 |
| abstract_inverted_index.sequenced | 166 |
| abstract_inverted_index.signature | 161, 233 |
| abstract_inverted_index.validated | 157 |
| abstract_inverted_index.Background | 1 |
| abstract_inverted_index.Nanostring | 93 |
| abstract_inverted_index.carcinoma. | 112, 276 |
| abstract_inverted_index.containing | 98, 173 |
| abstract_inverted_index.dysplasia, | 65, 107, 109 |
| abstract_inverted_index.epithelial | 136, 213, 238, 256 |
| abstract_inverted_index.guidelines | 41 |
| abstract_inverted_index.high-grade | 108 |
| abstract_inverted_index.identified | 129 |
| abstract_inverted_index.pancreatic | 10, 22 |
| abstract_inverted_index.population | 30, 245 |
| abstract_inverted_index.precursors | 20 |
| abstract_inverted_index.represents | 31, 249 |
| abstract_inverted_index.sequencing | 116 |
| abstract_inverted_index.suggesting | 66 |
| abstract_inverted_index.undergoing | 258 |
| abstract_inverted_index.Conclusions | 223 |
| abstract_inverted_index.Intraductal | 4 |
| abstract_inverted_index.determining | 46 |
| abstract_inverted_index.investigate | 78 |
| abstract_inverted_index.isolation). | 188 |
| abstract_inverted_index.opportunity | 34 |
| abstract_inverted_index.progression | 259, 274 |
| abstract_inverted_index.single-cell | 164 |
| abstract_inverted_index.IPMN-bearing | 28 |
| abstract_inverted_index.IPMN-derived | 111 |
| abstract_inverted_index.demonstrates | 226 |
| abstract_inverted_index.identifiable | 19 |
| abstract_inverted_index.insufficient | 43 |
| abstract_inverted_index.progression, | 86 |
| abstract_inverted_index.transitional | 251 |
| abstract_inverted_index.biospecimens. | 126 |
| abstract_inverted_index.distribution. | 222 |
| abstract_inverted_index.interception, | 39 |
| abstract_inverted_index.overtreatment | 71 |
| abstract_inverted_index.subpopulation | 131, 236 |
| abstract_inverted_index.surveillance, | 53 |
| abstract_inverted_index.KRT17-positive | 202 |
| abstract_inverted_index.adenocarcinoma | 24 |
| abstract_inverted_index.histologically | 133, 216, 241, 254 |
| abstract_inverted_index.radiologically | 18 |
| abstract_inverted_index.transcriptional | 80, 141, 232 |
| abstract_inverted_index.transcriptomics | 90 |
| abstract_inverted_index.Immunofluorescence | 189 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5017197654 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 22 |
| corresponding_institution_ids | https://openalex.org/I27837315 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.6899999976158142 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.11777994 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |