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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 
Citation
 GENOME MEDICINE, Vol.16(1) : 20, 2024-01 
Journal Title
GENOME MEDICINE
Issue Date
2024-01
MeSH
Carcinoma, Pancreatic Ductal* / genetics ; DNA-Binding Proteins / genetics ; Gene Expression Profiling ; Humans ; Pancreatic Neoplasms* / genetics ; Pancreatic Neoplasms* / pathology ; Prognosis ; Single-Cell Analysis ; Transcription Factors / genetics ; Transcriptome ; Tumor Microenvironment / genetics
Keywords
Cancer-associated fibroblasts ; Molecular subtype of pancreatic cancer ; Pancreatic cancer ; Pancreatic cancer cells ; Transitional cell state
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.
Files in This Item:
T202401112.pdf Download
DOI
10.1186/s13073-024-01287-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Chang Moo(강창무) ORCID logo https://orcid.org/0000-0002-5382-4658
Park, Seung Woo(박승우) ORCID logo https://orcid.org/0000-0001-8230-964X
Park, Jeong Youp(박정엽) ORCID logo https://orcid.org/0000-0003-0110-8606
Park, Chan Hee(박찬희)
Bang, Seungmin(방승민) ORCID logo https://orcid.org/0000-0001-5209-8351
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
Lee, Hee Seung(이희승) ORCID logo https://orcid.org/0000-0002-2825-3160
Leem, Ga Lam(임가람) ORCID logo https://orcid.org/0000-0001-6490-0911
Chung, Moon Jae(정문재) ORCID logo https://orcid.org/0000-0002-5920-8549
Jo, Jung Hyun(조중현) ORCID logo https://orcid.org/0000-0002-2641-8873
Hwang, Ho Kyoung(황호경) ORCID logo https://orcid.org/0000-0003-4064-7776
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198653
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