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Early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis

Authors
 Eun Young Kim  ;  Yoon Jin Cha  ;  Sang Hoon Lee  ;  Sukin Jeong  ;  Yong Jun Choi  ;  Duk Hwan Moon  ;  Sungsoo Lee  ;  Yoon Soo Chang 
Citation
 TRANSLATIONAL ONCOLOGY, Vol.15(1) : 101277, 2022-01 
Journal Title
TRANSLATIONAL ONCOLOGY
Issue Date
2022-01
Keywords
Early lung cancer ; Never smoker ; Single-cell RNA sequencing ; Tumor microenvironment
Abstract
With the increasing interest in health screening with chest CT Ground-glass nodule (GGN) has become one of the common lung lesions encountered in daily medical practice. Because lung adenocarcinoma in the form of GGN is an ideal model for studying early lung carcinogenesis, 11 GGN and normal lung specimens from 6 never smoker patients were studied by single-cell RNA sequencing. Lung cancer cells showed enrichment of gene sets related to small vesicle processing and surfactant homeostasis compared to non-malignant lung epithelial cells, suggesting the dysregulation of surfactant pathway may be involved in early lung carcinogenesis. Along with cancer-associated fibroblasts showing enrichment of gene sets involved in negative regulation of protein kinase activity and negative regulation of endothelial cell proliferation, tumor microenvironment (TME) was dominated by infiltration of TNFRSF4+/TNFRSF18+/CTLA4+ regulatory T cells (Treg) and depletion of CD8+ cytotoxic T cells (TC) and γδTC. Majority of mucosa-associated lymphoid tissue B cells (BCs) and follicular BCs were detected within tumor tissue, which was associated with CXCL13 overexpressed in intratumoral Tregs and CD4+ memory TCs. Coordination of components of the TME towards immune evasion is governed by Tregs from the onset of lung cancer, requiring unremitting efforts to target and overcome them. This provision of information on changes in cancer cell-specific biomarkers and TME using early lung cancer from never smokers will provide new insight into early lung carcinogenesis and useful targets for treatment.
Files in This Item:
T202201324.pdf Download
DOI
10.1016/j.tranon.2021.101277
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eun Young(김은영) ORCID logo https://orcid.org/0000-0002-3281-5744
Moon, Duk Hwan(문덕환)
Lee, Sang Hoon(이상훈) ORCID logo https://orcid.org/0000-0002-7706-5318
Lee, Sung Soo(이성수) ORCID logo https://orcid.org/0000-0001-8998-9510
Chang, Yoon Soo(장윤수) ORCID logo https://orcid.org/0000-0003-3340-4223
Chung, Sook In(정숙인) ORCID logo https://orcid.org/0000-0002-7915-9203
Cha, Yoon Jin(차윤진) ORCID logo https://orcid.org/0000-0002-5967-4064
Choi, Yong Jun(최용준) ORCID logo https://orcid.org/0000-0002-6114-2059
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188487
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