Satpathy, ShankhaShankhaSatpathyClark, Natalie MNatalie MClarkChen, Yi-JuYi-JuChenHosseini, NoshadNoshadHosseiniChang, Ya-HsuanYa-HsuanChangHsiao, YiYiHsiaoLei, Jonathan TJonathan TLeiPetralia, FrancescaFrancescaPetraliaJIN-SHING CHENGeffen, YifatYifatGeffenHeiman, David IDavid IHeimanPaul, IndranilIndranilPaulCho, HanbyulHanbyulChoHollenberg, MichelleMichelleHollenbergMarino, Giacomo BGiacomo BMarinoLin, Kuen-TyngKuen-TyngLinMannan, RahulRahulMannanWhite, C JacksonC JacksonWhiteAllen, JoeJoeAllenAvanessian, Shayan CShayan CAvanessianKane, M HarryM HarryKaneWolfe, AshleyAshleyWolfeKinarivala, MiloniMiloniKinarivalaLiu, WenkeWenkeLiuAnand, ShankaraShankaraAnandHaines, MoeMoeHainesMONG-WEI LINBergstrom, Erik JErik JBergstromHussey, GrantGrantHusseyLi, Ginny XiaoheGinny XiaoheLiMani, Deepak CDeepak CManiFang, HaoHaoFangJaehnig, Eric JEric JJaehnigKeshishian, HasmikHasmikKeshishianMiller, BreccaBreccaMillerHsiao, Yi-JingYi-JingHsiaoKANG-YI SUHsu, Kuo-HsuanKuo-HsuanHsuMonovoukas, AlexiAlexiMonovoukasMIN-SHU HSIEHGohsman, SimoneSimoneGohsmanThorup, John RJohn RThorupHSAO-HSUN HSUDeng, YameiYameiDengAkiyama, YoYoAkiyamaDeng, EdenEdenDengSheng-Wen Chen, EricEricSheng-Wen ChenKrek, AzraAzraKrekEspinoza, RodrigoRodrigoEspinozaMa, WeipingWeipingMaCharytonowicz, DanielDanielCharytonowiczSebra, RobertRobertSebraLin, Jyun-HongJyun-HongLinChen, Yan-SiYan-SiChenHsu, Yin-ChenYin-ChenHsuLin, Ze-ShiangZe-ShiangLinChen, Kun-ChiehKun-ChiehChenYeh, Chang-WeiChang-WeiYehWang, Yu-TaiYu-TaiWangLazar, Alexander JAlexander JLazarMesri, MehdiMehdiMesriAn, EunkyungEunkyungAnClauser, Karl RKarl RClauserFenyö, DavidDavidFenyöChinnaiyan, Arul MArul MChinnaiyanZhang, BingBingZhangXU-HENG CHIANGDing, LiLiDingRuggles, KellyKellyRugglesNewton, ChelseaChelseaNewtonZhang, HuiHuiZhangWang, PeiPeiWangHostetter, GalenGalenHostetterOmenn, Gilbert SGilbert SOmennKumar-Sinha, ChandanChandanKumar-SinhaThiagarajan, MathangiMathangiThiagarajanGovindan, RamaswamyRamaswamyGovindanPaik, PaulPaulPaikParolia, AbhijitAbhijitParoliaLi, Qing KQing KLiMa'ayan, AviAviMa'ayanGetz, Gad AGad AGetzDhanasekaran, Saravana MSaravana MDhanasekaranRobles, Ana IAna IRoblesChang, Gee-ChenGee-ChenChangChen, Hsuan-YuHsuan-YuChenPAN-CHYR YANGNesvizhskii, Alexey IAlexey INesvizhskiiCarr, Steven ASteven ACarrMani, D RD RManiCieslik, Marcin PMarcin PCieslikSUNG-LIANG YUChen, Yu-JuYu-JuChenGillette, Michael AMichael AGilletteCHAO-WEN LUPEI-HSING CHENet al.2025-09-042025-09-042025-07-30https://scholars.lib.ntu.edu.tw/handle/123456789/731779Lung adenocarcinomas (LUAD) are a pressing global health problem with enduring lethality and rapidly shifting epidemiology. Proteogenomic studies integrating proteomics and post-translational modifications with genomics can identify clinical strata and oncogenic mechanisms, but have been underpowered to examine effects of ethnicity, smoking and environmental exposures, or sex on this heterogeneous disease. This comprehensive proteogenomic analysis of LUAD tumors and matched normal adjacent tissues from 406 patients across diverse geographic and demographic backgrounds explores the impact of understudied driver mutations, prognostic role of chromosomal instability, patterns of immune signaling, differential and sex-specific effects of endogenous mutagens and environmental carcinogens, and pathobiology of early-stage tumors with "late-like" characteristics. Candidate protein biomarkers are proposed for unstable tumors with highly fragmented genomes and for carcinogen exposures, and a LUAD subtype-specific atlas of therapeutic vulnerabilities is presented. These observations and the associated data resource advance the objective of precision management strategies for this devastating disease.enCPTACICPCPTMsbiomarkersgenomicslung adenocarcinomamass spectrometrynever-smokersproteogenomicssmokers[SDGs]SDG3journal article10.1016/j.ccell.2025.07.01140749670