ArticlebioRxiv : the preprint server for biology2025
A prognostic signature for lung adenocarcinoma in people who have never smoked.
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69 authors.
Wei ZhaoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Tongwu ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Xing HuaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Phuc H HoangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Mona MiraftabDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Monjoy SahaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
John P McElderryDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Jian SangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Olivia W LeeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Caleb HartmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Azhar KhandekarDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Sunandini SharmaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Frank J Colón-MatosDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Samuel Anyaso-SamuelDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Difei WangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Kristine JonesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Amy HutchinsonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Belynda HicksDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Jennifer RosenbaumWestat, Rockville, MD, USA.
Xiaoming ZhongBen May Department for Cancer Research, Department of Human Genetics, Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
Yang YangBen May Department for Cancer Research, Department of Human Genetics, Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
Angela PesatoriDepartment of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Dario ConsonniFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
David C ChristianiDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Kin Chung LeungDepartment of Pathology, The University of Hong Kong, Hongkong, China.
Maria Pik WongQueen Mary Hospital, The University of Hong Kong, Hongkong, China.
Marta ManczukDepartment of Cancer Epidemiology and Primary Prevention, Maria Skłodowska-Curie National Research Institute of Oncology, Warshaw, Poland.
Jolanta LissowskaDepartment of Cancer Epidemiology and Primary Prevention, Maria Skłodowska-Curie National Research Institute of Oncology, Warshaw, Poland.
Beata ŚwiątkowskaDepartment of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Łódź, Poland.
Anush MukeriaDepartment of Clinical Epidemiology, N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russia.
Oxana ShanginaDepartment of Clinical Epidemiology, N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russia.
David ZaridzeDepartment of Clinical Epidemiology, N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russia.
Ivana HolcatovaInstitute of Public Health & Preventive Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
Dana MatesDepartment of Occupational Health and Toxicology, National Center for Environmental Risk Monitoring, National Institute of Public Health, Bucharest, Romania.
Sasa MilosavljevicInternational Organisation for Cancer Prevention and Research (IOCPR), Belgrade, Serbia.
Simona OgnjanovicInternational Organisation for Cancer Prevention and Research (IOCPR), Belgrade, Serbia.
Milan SavicDepartment of Thoracic Surgery, Clinical Center of Serbia, Belgrade, Serbia.
Millica KonticClinic of Pulmonology, Clinical Center of Serbia, Belgrade, Serbia.
Valerie GaborieauGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Paul BrennanGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
Oscar ArrietaThoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Yohan BosséInstitut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada.
Eric S EdellDivision of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
Matthew B SchabathDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.ORCID 0000-0003-3241-3216
Paul HofmanIHU RespirERA, Biobank-BB-0033-0025, Côte d'Azur University, Nice, France.
Luis MasMedical Oncology Unit, Instituto Nacional de Enfermedades Neoplásicas (INEN), Lima, Peru.
Sai S YendamuriThoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Chih-Yi ChenInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
I-Shou ChangNational Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
Chao Agnes HsiungInstitute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Geoffrey LiuDivision of Medical Oncology, Medicine, Princess Margaret Cancer Centre, Temerty Faculty of Medicine, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Jacobo Martínez SantamaríaBiobanco IBSP-CV FISABIO, Red Valenciana de Biobancos, Cataluña, Valencia, Spain.
Bonnie E Gould RothbergSylvester Comprehensive Cancer Center, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
Karun MutrejaMolecular and Digital Pathology Laboratory, Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Scott LawrenceNational Cancer Institute, Bethesda, MD, USA.
Nathaniel RothmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Ludmil B AlexandrovDepartment of Cellular and Molecular Medicine and Department of Bioengineering and Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0003-3596-4515
Charles LeducDepartment of Pathology, Centre Hospitalier de l'Université de Montréal, Montreal, Canada.
Marina K BaineDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Philippe JoubertInstitut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada.
Lynette M ShollDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
William D TravisDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Robert HomerDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Qing LanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Lixing YangBen May Department for Cancer Research, Department of Human Genetics, Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
Soo-Ryum YangDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jianxin ShiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Maria Teresa LandiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MTRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5MStudies of Genetic and Environmental EpidemiologyZIACP101231 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI LANDI, MARIA · 2018 to 2025
$23.6MThe Boston Lung Cancer Survival CohortU01CA209414 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI David C Christiani · 2017 to 2026
$12.2MIntramural NIH HHS ZIA CP101231NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA076292NCI NIH HHS U01 CA209414
Abstract
Knowledge of tumor cell dynamics can inform prognosis and treatment yet is largely lacking for lung adenocarcinoma in people who have never smoked (NS-LUAD). With RNA-seq data from 684 NS-LUAD and validation in an independent dataset, we identified three subtypes with distinct phenotypic traits and cell compositions. Additional genomic and histological data further characterized the subtypes.
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