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Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages

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资源类型：
Pubmed体系：
作者：
Deng Yulan[1,2] * ; Xia Liang[1,2] * ; Zhang Jian[1,2] * ; Deng Senyi[1,2] * ; Wang Mengyao[1,2,3] ; Wei Shiyou[1,2] ; Li Kaixiu[1,2,3] ; Lai Hongjin[1,2] ; Yang Yunhao[1,2] ; Bai Yuquan[1,2] ; Liu Yongcheng[1,2] ; Luo Lanzhi[1,2] ; Yang Zhenyu[1,2] ; Chen Yaohui[1,2] ; Kang Ran[1,2] ; Gan Fanyi[1,2] ; Pu Qiang[1,2] ; Mei Jiandong[1,2] ; Ma Lin[1,2] ; Lin Feng[1,2] ; Guo Chenglin[1,2] ; Liao Hu[1,2] ; Zhu Yunke[1,2] ; Liu Zheng[1,2] ; Liu Chengwu[1,2] ; Hu Yang[1,2] ; Yuan Yong[1,2] ; Zha Zhengyu[1,2] ; Yuan Gang[1,2] ; Zhang Gao[3] ; Chen Luonan[4,5,6] ; Cheng Qing[7] ; Shen Shensi[1,2] ; Liu Lunxu[1,2] ;
机构： [1]Department of Thoracic Surgery and Institute of Thoracic Oncology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China [2]Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu 610041, China [3]Faculty of Dentistry, The University of Hong Kong, Prince Philip Dental Hospital, Sai Ying Pun, Hong Kong, China [4]State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China [5]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China [6]Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China [7]Department of Surgery, Duke University School of Medicine, Durham, NC, USA
出处：
DOI： 10.1016/j.xcrm.2024.101489

摘要：
Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8+ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8+ T cells, driven by specific stromal cells such as CTHCR1+ fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8+ T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

基金：
L. Liu holds a National Key Research and Development Program of China grant (no. 2022YFC3400405) and holds financial supports ZYGD18021 and ZYJC21002, supported by the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University, as well as grant 2021YFS0024, supported by the major research project of Sichuan Province, China. S.S. holds a grant from the Natural Science Foundation of China (no. 82172794) and a grant from the National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (no. Y2022JC002) and gives thanks for the generous support from Se´ bastien Bazin (France). J.M. holds a grant (ZYJC18009) supported by the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University. Y.C. holds a grant (ZYJC21015) supported by the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验 2 区 细胞生物学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验 2 区 细胞生物学
第一作者：
第一作者机构： [1]Department of Thoracic Surgery and Institute of Thoracic Oncology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China [2]Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu 610041, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Thoracic Surgery and Institute of Thoracic Oncology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China [2]Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu 610041, China
推荐引用方式(GB/T 7714)：
Deng Yulan,Xia Liang,Zhang Jian,et al.Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages[J].Cell Reports. Medicine.2024,5(4):101489.doi:10.1016/j.xcrm.2024.101489.
APA：
Deng Yulan,Xia Liang,Zhang Jian,Deng Senyi,Wang Mengyao...&Liu Lunxu.(2024).Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.Cell Reports. Medicine,5,(4)
MLA：
Deng Yulan,et al."Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages".Cell Reports. Medicine 5..4(2024):101489

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