BACKGROUND: Lung adenocarcinoma (LUAD) patients with different American Joint Committee on Cancer stages have different overall 5-year survival rates. The tumor microenvironment (TME) and intra-tumor heterogeneity (ITH) have been shown to play a crucial role in the occurrence and development of tumors. However, the TME and ITH in different lesions of LUAD have not been extensively explored. METHODS: We present a 204,157-cell catalog of the TME transcriptome in 29 lung samples to systematically explore the TME and ITH in the different stages of LUAD. Traditional RNA sequencing data and complete clinical information were downloaded from publicly available databases. RESULTS: Based on these high-quality cells, we constructed a single-cell network underlying cellular and molecular features of normal lung, early LUAD, and advanced LUAD cells. In contrast with early malignant cells, we noticed that advanced malignant cells had a remarkably more complex TME and higher ITH level. We also found that compared with other immune cells, more differences in CD8+/CTL T cells, regulatory T cells, and follicular B cells were evident between early and advanced LUAD. Additionally, cell-cell communication analyses, revealed great diversity between different lesions of LUAD at the single-cell level. Flow cytometry and qRT-PCR were used to validate our results. CONCLUSION: Our results revealed the cellular diversity and molecular complexity of cell lineages in different stages of LUAD. We believe our research, which serves as a basic framework and valuable resource, can facilitate exploration of the pathogenesis of LUAD and identify novel therapeutic targets in the future.
BACKGROUND: Lung adenocarcinoma (LUAD) patients with different American Joint Committee on Cancer stages have different overall 5-year survival rates. The tumor microenvironment (TME) and intra-tumor heterogeneity (ITH) have been shown to play a crucial role in the occurrence and development of tumors. However, the TME and ITH in different lesions of LUAD have not been extensively explored. METHODS: We present a 204,157-cell catalog of the TME transcriptome in 29 lung samples to systematically explore the TME and ITH in the different stages of LUAD. Traditional RNA sequencing data and complete clinical information were downloaded from publicly available databases. RESULTS: Based on these high-quality cells, we constructed a single-cell network underlying cellular and molecular features of normal lung, early LUAD, and advanced LUAD cells. In contrast with early malignant cells, we noticed that advanced malignant cells had a remarkably more complex TME and higher ITH level. We also found that compared with other immune cells, more differences in CD8+/CTL T cells, regulatory T cells, and follicular B cells were evident between early and advanced LUAD. Additionally, cell-cell communication analyses, revealed great diversity between different lesions of LUAD at the single-cell level. Flow cytometry and qRT-PCR were used to validate our results. CONCLUSION: Our results revealed the cellular diversity and molecular complexity of cell lineages in different stages of LUAD. We believe our research, which serves as a basic framework and valuable resource, can facilitate exploration of the pathogenesis of LUAD and identify novel therapeutic targets in the future.
Authors: Ke-Yue Ma; Alexandra A Schonnesen; Amy Brock; Carla Van Den Berg; S Gail Eckhardt; Zhihua Liu; Ning Jiang Journal: JCI Insight Date: 2019-02-21
Authors: Ashley M Laughney; Jing Hu; Nathaniel R Campbell; Samuel F Bakhoum; Manu Setty; Vincent-Philippe Lavallée; Yubin Xie; Ignas Masilionis; Ambrose J Carr; Sanjay Kottapalli; Viola Allaj; Marissa Mattar; Natasha Rekhtman; Joao B Xavier; Linas Mazutis; John T Poirier; Charles M Rudin; Dana Pe'er; Joan Massagué Journal: Nat Med Date: 2020-02-10 Impact factor: 53.440
Authors: Cyril Neftel; Julie Laffy; Mariella G Filbin; Toshiro Hara; Marni E Shore; Gilbert J Rahme; Alyssa R Richman; Dana Silverbush; McKenzie L Shaw; Christine M Hebert; John Dewitt; Simon Gritsch; Elizabeth M Perez; L Nicolas Gonzalez Castro; Xiaoyang Lan; Nicholas Druck; Christopher Rodman; Danielle Dionne; Alexander Kaplan; Mia S Bertalan; Julia Small; Kristine Pelton; Sarah Becker; Dennis Bonal; Quang-De Nguyen; Rachel L Servis; Jeremy M Fung; Ravindra Mylvaganam; Lisa Mayr; Johannes Gojo; Christine Haberler; Rene Geyeregger; Thomas Czech; Irene Slavc; Brian V Nahed; William T Curry; Bob S Carter; Hiroaki Wakimoto; Priscilla K Brastianos; Tracy T Batchelor; Anat Stemmer-Rachamimov; Maria Martinez-Lage; Matthew P Frosch; Ivan Stamenkovic; Nicolo Riggi; Esther Rheinbay; Michelle Monje; Orit Rozenblatt-Rosen; Daniel P Cahill; Anoop P Patel; Tony Hunter; Inder M Verma; Keith L Ligon; David N Louis; Aviv Regev; Bradley E Bernstein; Itay Tirosh; Mario L Suvà Journal: Cell Date: 2019-07-18 Impact factor: 41.582