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

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 sp...

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Autores principales:	Eun Young Kim, Yoon Jin Cha, Sang Hoon Lee, Sukin Jeong, Yong Jun Choi, Duk Hwan Moon, Sungsoo Lee, Yoon Soo Chang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Never smoker Early lung cancer Single-cell RNA sequencing Tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c525bd71c1894af8a985344c6071bc8c
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spelling	oai:doaj.org-article:c525bd71c1894af8a985344c6071bc8c2021-11-20T05:05:18ZEarly lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis1936-523310.1016/j.tranon.2021.101277https://doaj.org/article/c525bd71c1894af8a985344c6071bc8c2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1936523321002680https://doaj.org/toc/1936-5233With 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.Eun Young KimYoon Jin ChaSang Hoon LeeSukin JeongYong Jun ChoiDuk Hwan MoonSungsoo LeeYoon Soo ChangElsevierarticleNever smokerEarly lung cancerSingle-cell RNA sequencingTumor microenvironmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENTranslational Oncology, Vol 15, Iss 1, Pp 101277- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Never smoker Early lung cancer Single-cell RNA sequencing Tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Never smoker Early lung cancer Single-cell RNA sequencing Tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Eun Young Kim Yoon Jin Cha Sang Hoon Lee Sukin Jeong Yong Jun Choi Duk Hwan Moon Sungsoo Lee Yoon Soo Chang Early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis
description	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.
format	article
author	Eun Young Kim Yoon Jin Cha Sang Hoon Lee Sukin Jeong Yong Jun Choi Duk Hwan Moon Sungsoo Lee Yoon Soo Chang
author_facet	Eun Young Kim Yoon Jin Cha Sang Hoon Lee Sukin Jeong Yong Jun Choi Duk Hwan Moon Sungsoo Lee Yoon Soo Chang
author_sort	Eun Young Kim
title	Early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis
title_short	Early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis
title_full	Early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis
title_fullStr	Early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis
title_full_unstemmed	Early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis
title_sort	early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/c525bd71c1894af8a985344c6071bc8c
work_keys_str_mv	AT eunyoungkim earlylungcarcinogenesisandtumormicroenvironmentobservedbysinglecelltranscriptomeanalysis AT yoonjincha earlylungcarcinogenesisandtumormicroenvironmentobservedbysinglecelltranscriptomeanalysis AT sanghoonlee earlylungcarcinogenesisandtumormicroenvironmentobservedbysinglecelltranscriptomeanalysis AT sukinjeong earlylungcarcinogenesisandtumormicroenvironmentobservedbysinglecelltranscriptomeanalysis AT yongjunchoi earlylungcarcinogenesisandtumormicroenvironmentobservedbysinglecelltranscriptomeanalysis AT dukhwanmoon earlylungcarcinogenesisandtumormicroenvironmentobservedbysinglecelltranscriptomeanalysis AT sungsoolee earlylungcarcinogenesisandtumormicroenvironmentobservedbysinglecelltranscriptomeanalysis AT yoonsoochang earlylungcarcinogenesisandtumormicroenvironmentobservedbysinglecelltranscriptomeanalysis
_version_	1718419621591121920

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

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