Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma. - Literature - Data resources

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Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma.

Nat Commun, 2020/05/08;11(1):2285.

Kim N^{[1, 2, 3]}, Kim HK^[4], Lee K^[5], Hong Y^{[1, 6]}, Cho JH^[4], Choi JW^[7], Lee JI^[7], Suh YL^[8], Ku BM^[9], Eum HH^{[1, 2, 3]}, Choi S^[1], Choi YL^{[6, 10, 11]}, Joung JG^[1], Park WY^{[1, 2, 6]}, Jung HA^[12], Sun JM^[12], Lee SH^[12], Ahn JS^[12], Park K^[12], Ahn MJ^[13], Lee HO^{[14, 15, 16, 17]}

Affiliations

Samsung Genome Institute, Samsung Medical Center, Seoul, 06351, Korea.
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, Korea.
Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, 06591, Korea.
Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 06351, Seoul, Korea.
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences &Technology, Sungkyunkwan University, Seoul, 06355, Korea.
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Division of Haematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Division of Haematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea. silk.ahn@samsung.com.
Samsung Genome Institute, Samsung Medical Center, Seoul, 06351, Korea. haeocklee@catholic.ac.kr.
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, Korea. haeocklee@catholic.ac.kr.
Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, 06591, Korea. haeocklee@catholic.ac.kr.
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences &Technology, Sungkyunkwan University, Seoul, 06355, Korea. haeocklee@catholic.ac.kr.

PMID: 32385277DOI: 10.1038/s41467-020-16164-1

Impact factor: 17.694

Abstract

Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell transcriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions.

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