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

Autor: Kim S; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 34141, Republic of Korea., Leem G; Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea., Choi J; Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea., Koh Y; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 34141, Republic of Korea., Lee S; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 34141, Republic of Korea., Nam SH; Department of Internal Medicine, Graduate School of Yonsei University, Seoul, Republic of Korea., Kim JS; Department of Internal Medicine, Graduate School of Yonsei University, Seoul, Republic of Korea., Park CH; Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea., Hwang HK; Division 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.; Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Republic of Korea., Min KI; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 34141, Republic of Korea., Jo JH; Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea., Lee HS; Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea., Chung MJ; Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea., Park JY; Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea., Park SW; Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea., Song SY; Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea., Shin EC; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 34141, Republic of Korea., Kang CM; Division 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. cmkang@yuhs.ac.; Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Republic of Korea. cmkang@yuhs.ac., Bang S; Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea. bang7028@yuhs.ac., Park JE; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 34141, Republic of Korea. jp24@kaist.ac.kr.
Jazyk: angličtina
Zdroj: Genome medicine [Genome Med] 2024 Jan 31; Vol. 16 (1), pp. 20. Date of Electronic Publication: 2024 Jan 31.
DOI: 10.1186/s13073-024-01287-7
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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