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

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...

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Bibliographic Details
Published in:Genome Medicine 2024, Vol.16 (1)
Main Authors: Kim, Seongryong, Leem, Galam, Choi, Junjeong, Koh, Yongjun, Lee, Suho, Nam, Sang-Hee, Kim, Jin Su, Park, Chan Hee, Hwang, Ho Kyoung, Min, Kyoung Il, Jo, Jung Hyun, Lee, Hee Seung, Chung, Moon Jae, Park, Jeong Youp, Park, Seung Woo, Song, Si Young, Shin, Eui-Cheol, Kang, Chang Moo, Bang, Seungmin, Park, Jong-Eun
Format: Report
Language:English
Subjects:
Analysis
Cancer
Dysplasia
Health aspects
Oncology, Experimental
Pancreatic cancer
RNA
RNA sequencing
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Summary: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 Keywords: Pancreatic cancer, Pancreatic cancer cells, Transitional cell state, Molecular subtype of pancreatic cancer, Cancer-associated fibroblasts
ISSN:1756-994X
1756-994X
DOI:10.1186/s13073-024-01287-7