{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T23:54:05Z","timestamp":1784418845130,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2500903"],"award-info":[{"award-number":["2021YFC2500903"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072557"],"award-info":[{"award-number":["82072557"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The presence of lymph node (LN) metastasis directly affects the treatment strategy for lung adenocarcinoma (LUAD). Next\u2010generation sequencing (NGS) has been widely used in patients with advanced LUAD to identify targeted genes, while early detection of pathologic LN metastasis using NGS has not been assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinicopathologic features and molecular characteristics of 224 patients from Ruijin Hospital were analyzed to detect factors associated with LN metastases. Another 140 patients from Huashan Hospital were set as a test cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010four out of 224 patients were found to have lymph node metastases (10.7%). Pathologic LN\u2010positive tumors showed higher mutant allele tumor heterogeneity (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), higher tumor mutation burden (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), as well as more frequent KEAP1 (<jats:italic>p<\/jats:italic>\u2009=\u20090.001), STK11 (<jats:italic>p<\/jats:italic>\u2009=\u20090.004), KRAS (<jats:italic>p<\/jats:italic>\u2009=\u20090.007), CTNNB1 (<jats:italic>p<\/jats:italic>\u2009=\u20090.017), TP53, and ARID2 mutations (both <jats:italic>p<\/jats:italic>\u2009=\u20090.02); whereas low frequency of EGFR mutation (<jats:italic>p<\/jats:italic>\u2009=\u20090.005). A predictive nomogram involving male sex, solid tumor morphology, higher T stage, EGFR wild\u2010type, and TP53, STK11, CDKN2A, KEAP1, ARID2, KRAS, SDHA, SPEN, CTNNB1, DICER1 mutations showed outstanding efficiency in both the training cohort (AUC\u2009=\u20090.819) and the test cohort (AUC\u2009=\u20090.780).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study suggests that the integration of genomic profiling and clinical features identifies early\u2010invasive LUAD patients at higher risk of LN metastasis. Improved identification of LN metastasis is beneficial for the optimization of the patient's therapy decisions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70039","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T12:25:03Z","timestamp":1721823903000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lymph node metastasis in early invasive lung adenocarcinoma: Prediction model establishment and validation based on genomic profiling and clinicopathologic characteristics"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7532-2217","authenticated-orcid":false,"given":"Wei","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6259-5070","authenticated-orcid":false,"given":"Tong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Huashan Hospital, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9952-0425","authenticated-orcid":false,"given":"Xijia","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingpei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debin","family":"Sun","sequence":"additional","affiliation":[{"name":"Genecast Biotechnology Co., Ltd  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Gong","sequence":"additional","affiliation":[{"name":"Genecast Biotechnology Co., Ltd  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengqiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runsen","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbiao","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Huashan Hospital, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8069-6033","authenticated-orcid":false,"given":"Hecheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33588"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62159-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcts.2009.04.013"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-018-4848-7"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5223(99)70340-5"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2020-0905"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-015-5043-9"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.35.15_suppl.11570"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.202.2.9015071"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900043"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078552"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2018.12.041"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3182992421"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-020-07466-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crad.2022.08.140"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2013.06.038"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.3239"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2019.06.026"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-021-00210-2"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_10_23_1","volume-title":"Broad Institute, GitHub Repository","author":"Picard Toolkit","year":"2019"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw227"},{"key":"e_1_2_10_26_1","unstructured":"GarrisonE MarthG.Haplotype\u2010based variant detection from short\u2010read sequencing. arXiv preprint arXiv:1207.3907 [q\u2010bio.GN]2012."},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004873"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-4-r41"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2019.10.072"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezaa138"},{"key":"e_1_2_10_31_1","first-page":"299","article-title":"Ueber asymmetrische Zelltheilung in Epithelkrebsen und deren biologische Bedeutung","volume":"119","author":"Hansemann D","year":"1890","journal-title":"Archiv f\u00fcr Pathologische Anatomie Und Physiologie Und f\u00fcr Klinische Medicin"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2037"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2009.02.017"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1556-0864(15)31573-2"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2020.05.041"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resinv.2013.02.004"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143515"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jons.2019.08.002"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezw362"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.12.008"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06030"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2019.01.020"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0099"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2022.07.014"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajco.13934"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.08.014"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15092491"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semnuclmed.2020.09.001"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-022-09153-z"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0624"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00241"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14112"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.70039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T22:45:45Z","timestamp":1744929945000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.70039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":51,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/cam4.70039"],"URL":"https:\/\/doi.org\/10.1002\/cam4.70039","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"2024-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70039"}}