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Integrative analysis of spatial and single-cell transcriptome data from human pancreatic cancer reveals an intermediate cancer cell population associated with poor prognosis.

Authors :
Kim S
Leem G
Choi J
Koh Y
Lee S
Nam SH
Kim JS
Park CH
Hwang HK
Min KI
Jo JH
Lee HS
Chung MJ
Park JY
Park SW
Song SY
Shin EC
Kang CM
Bang S
Park JE
Source :
Genome medicine [Genome Med] 2024 Jan 31; Vol. 16 (1), pp. 20. Date of Electronic Publication: 2024 Jan 31.
Publication Year :
2024

Abstract

Background: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity.<br />Methods: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples.<br />Results: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data.<br />Conclusions: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets.<br /> (© 2024. The Author(s).)

Details

Language :
English
ISSN :
1756-994X
Volume :
16
Issue :
1
Database :
MEDLINE
Journal :
Genome medicine
Publication Type :
Academic Journal
Accession number :
38297291
Full Text :
https://doi.org/10.1186/s13073-024-01287-7