{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:43:07Z","timestamp":1787920987766,"version":"build-2784847793"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802255"],"award-info":[{"award-number":["81802255"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small Methods"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lung cancer remains the leading cause of cancer\u2010related death worldwide. Lung adenocarcinoma (LUAD) is thought to be caused by precursor lesions of atypical adenoma\u2010like hyperplasia and may have extensive in situ growth before infiltration. To explore the relevant factors in heterogeneity and evolution of lung adenocarcinoma subtypes, the authors perform single\u2010cell RNA sequencing (scRNA\u2010seq) on tumor and normal tissue from five multiple nodules\u2019 LUAD patients and conduct a thorough gene expression profiling of cancer cells and cells in their microenvironment at single\u2010cell level. This study gives a deep understanding of heterogeneity and evolution in early glandular neoplasia of the lung. This dataset leads to discovery of the changes in the immune microenvironment during the development of LUAD, and the development process from adenocarcinoma in situ (AIS) to invasive adenocarcinoma (IAC). This work sheds light on the direction of early tumor development and whether they are homologous.<\/jats:p>","DOI":"10.1002\/smtd.202100082","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T11:52:36Z","timestamp":1618833156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Mechanisms of Progression and Heterogeneity in Multiple Nodules of Lung Adenocarcinoma"],"prefix":"10.1002","volume":"5","author":[{"given":"Yayi","family":"He","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Surgery Shanghai Pulmonary Hospital Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Surgery Shanghai Pulmonary Hospital Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minlin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyue","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Surgery Shanghai Pulmonary Hospital Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanhao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Surgery Shanghai Pulmonary Hospital Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7095-0381","authenticated-orcid":false,"given":"Caicun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Shanghai Pulmonary Hospital Tongji University Medical School Cancer Institute Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Surgery Shanghai Pulmonary Hospital Tongji University School of Medicine  No 507 Zhengmin Road Shanghai 200433 China"},{"name":"School of Materials Science and Engineering Tongji University  Shanghai 201804 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2016.03.009"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.073"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16295-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01528-0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2019.07.031"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2113"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0045-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.014"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0096-5"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214865"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.65.12.5052-5056.1997"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573407210666140311234806"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.5.12.3354"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1733"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207433"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3030681"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(98)00083-1"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2016.05.001"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11121832"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-13-0117"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3671"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.14"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-1342"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2016.01.005"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.2000.01517.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.01.022"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI125669"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040035"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.20"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11040470"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.3.1534"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.07.009"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0214"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22681"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.2.7633739"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv100"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.05.017"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2018.02.016"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt356"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22323"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818210116"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3727\/096504018X15372657298381"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22323"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-014-0087-z"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.07.007"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0472-6"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1794"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-1569"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e318189f5ec"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2018.01.012"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-020-03194-x"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.104129"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.549213"}],"container-title":["Small Methods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smtd.202100082","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/smtd.202100082","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smtd.202100082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T10:44:33Z","timestamp":1693392273000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smtd.202100082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/smtd.202100082"],"URL":"https:\/\/doi.org\/10.1002\/smtd.202100082","archive":["Portico"],"relation":{},"ISSN":["2366-9608","2366-9608"],"issn-type":[{"value":"2366-9608","type":"print"},{"value":"2366-9608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,19]]},"assertion":[{"value":"2021-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2100082"}}