한빛사논문
- 조회465
Seongryong Kim # 1, Galam Leem # 2, Junjeong Choi 3, Yongjun Koh 1, Suho Lee 1, Sang-Hee Nam 4, Jin Su Kim 4, Chan Hee Park 2, Ho Kyoung Hwang 5 6, Kyoung Il Min 1, Jung Hyun Jo 2, Hee Seung Lee 2, Moon Jae Chung 2, Jeong Youp Park 2, Seung Woo Park 2, Si Young Song 2, Eui-Cheol Shin 1, Chang Moo Kang 7 8 *, Seungmin Bang 9 *, Jong-Eun Park 10 *
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 34141, Republic of Korea.
2Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
3Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea.
4Department of Internal Medicine, Graduate School of Yonsei University, Seoul, Republic of Korea.
5Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, Pancreatobiliary Cancer Center, Severance Hospital, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
6Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Republic of Korea.
7Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, Pancreatobiliary Cancer Center, Severance Hospital, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
8Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Republic of Korea.
9Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
10Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 34141, Republic of Korea.
#Contributed equally
*Corresponding authors: correspondence to Chang Moo Kang, Seungmin Bang or Jong-Eun Park
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.
논문정보
- Research article
- 2024년 01월 (BRIC 등록일 2024-02-01)
- 국내 연구진
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