Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes  

作　　者：Sahil Seth Runzhe Chen Yang Liu Junya Fujimoto Lingzhi Hong Alexandre Reuben Susan Varghese Carmen Behrens Tina McDowell Luisa Solis Soto Cara Haymaker Annikka Weissferdt Neda Kalhor Jia Wu Xiuning Le Natalie I Vokes Chao Cheng John V.Heymach Don L.Gibbons P.Andrew Futreal Ignacio IWistuba Humam Kadara Jianhua Zhang Cesar Moran Jianjun Zhang 

机构地区：[1]Department of Genomic Medicine,The University of Texas MD Anderson Cancer Center,Houston,Texas,USA [2]TRACTION,The University of Texas MD Anderson Cancer Center,Houston,Texas,USA [3]Graduate School of Biomedical Sciences,The University of Texas MD Anderson and the University of Texas Health Science Center,Houston,Texas,USA [4]Department of Thoracic/Head and Neck Medical Oncology,The University of Texas MD Anderson Cancer Center,Houston,Texas,USA [5]Department of Translational Molecular Pathology,The University of Texas MD Anderson Cancer Center,Houston,Texas,USA [6]Department of Epidemiology,The University of Texas MD Anderson Cancer Center,Houston,Texas,USA [7]Department of Pathology,The University of Texas MD Anderson Cancer Center,Houston,Texas,USA [8]Department of Imaging Physics,The University of Texas MD Anderson Cancer Center,Houston,Texas,USA [9]Department of Medicine,Baylor College of Medicine,Houston,Texas,USA

出　　处：《Cancer Innovation》2024年第3期81-94,共14页肿瘤创新（英文）

基　　金：ASCO,Cancer Prevention&Research Institute of Texas(CPRIT),University Cancer Foundation,CPRIT Research Training Program,Grant/Award Number:RP170067;TJ Martell Foundation,NIH/NCI,Grant/Award Number:R01-CA207295;University of Texas MD Anderson Cancer Center,the Happy Lungs Project;Cancer Prevention&Research Institute of Texas;Rexanna's Foundation for Fighting Lung Cancer;Conquer Cancer Foundation;NIH/NCI,Grant/Award Number:U01-CA213273;Department of Defense,Grant/Award Number:LC170171;Damon Runyon Mark Foundation Physician Scientist Award,Rexanna Foundation,Grant/Award Number:R01 CA276178-01A1。

摘　　要：Background:Pulmonary sarcomatoid carcinoma(PSC)is a rare and aggressive subtype of non-small cell lung cancer(NSCLC),characterized by the presence of epithelial and sarcoma-like components.The molecular and immune landscape of PSC has not been well defined.Methods:Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel,whole-exome,and RNA sequencing.We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes.Results:In total,27 canonical cancer gene mutations were identified,with TP53 the most frequently mutated gene,followed by KRAS.Interestingly,most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors,suggesting branching evolution in most PSC tumors.We identified two distinct molecular subtypes of PSC,driven primarily by immune infiltration and signaling.The Immune High(IM-H)subtype was associated with superior survival,highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs.Conclusions:We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis.IM-H tumors were associated with favorable recurrence-free survival and overall survival,highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.

关 键 词：GENOMIC IMMUNE pulmonary sarcomatoid carcinoma survival 

分 类 号：R734.2[医药卫生—肿瘤]