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

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 sta...

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Vydané v:	Nature communications Ročník 11; číslo 1; s. 2285 - 15
Hlavní autori:	Kim, Nayoung, Kim, Hong Kwan, Lee, Kyungjong, Hong, Yourae, Cho, Jong Ho, Choi, Jung Won, Lee, Jung-Il, Suh, Yeon-Lim, Ku, Bo Mi, Eum, Hye Hyeon, Choi, Soyean, Choi, Yoon-La, Joung, Je-Gun, Park, Woong-Yang, Jung, Hyun Ae, Sun, Jong-Mu, Lee, Se-Hoon, Ahn, Jin Seok, Park, Keunchil, Ahn, Myung-Ju, Lee, Hae-Ock
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 08.05.2020 Nature Publishing Group Nature Portfolio
Predmet:	13/1 13/31 13/51 38/91 631/114/2164 631/67/1612/1350 631/67/2329 631/67/327 Adaptive Immunity Adenocarcinoma Adenocarcinoma of Lung - blood supply Adenocarcinoma of Lung - genetics Adenocarcinoma of Lung - immunology Adenocarcinoma of Lung - pathology Cell differentiation Cell Lineage Cellular Reprogramming - genetics Dendritic cells Diagnostic systems Disease Progression Endothelial Cells - pathology Exhaustion Gene expression Gene sequencing Humanities and Social Sciences Humans Immune system Ligands Lung cancer Lung Neoplasms - blood supply Lung Neoplasms - genetics Lung Neoplasms - immunology Lung Neoplasms - pathology Lymphocytes T Macrophages Metastases Metastasis Monocytes multidisciplinary Myeloid Cells - pathology Myofibroblasts - pathology Neoplasm Metastasis Neoplasm Staging Neovascularization, Pathologic - pathology Phenotype Receptors, Cell Surface - metabolism Ribonucleic acid RNA Science Science (multidisciplinary) Sequence Analysis, RNA Single-Cell Analysis Stromal Cells - metabolism Survival Analysis Therapeutic applications
ISSN:	2041-1723, 2041-1723
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Shrnutí:	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. Understanding the mechanisms that lead to lung adenocarcinoma metastasis is important for identifying new therapeutics. Here, the authors document the changes in the transcriptome of human lung adenocarcinoma using single-cell sequencing and link cancer cell signatures to immune cell dynamics.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-020-16164-1