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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 :
Seongryong Kim
Galam Leem
Junjeong Choi
Yongjun Koh
Suho Lee
Sang-Hee Nam
Jin Su Kim
Chan Hee Park
Ho Kyoung Hwang
Kyoung Il Min
Jung Hyun Jo
Hee Seung Lee
Moon Jae Chung
Jeong Youp Park
Seung Woo Park
Si Young Song
Eui-Cheol Shin
Chang Moo Kang
Seungmin Bang
Jong-Eun Park
Source :
Genome Medicine, Vol 16, Iss 1, Pp 1-18 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

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. 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. 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. 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. Graphical Abstract

Details

Language :
English
ISSN :
1756994X
Volume :
16
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Genome Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.1c44fc99a70f419f9ea61b463f3a7c7e
Document Type :
article
Full Text :
https://doi.org/10.1186/s13073-024-01287-7