Proteogenomic analysis of lung adenocarcinoma reveals tumor heterogeneity, survival determinants, and therapeutically relevant pathways

• DOI: 10.1016/j.xcrm.2022.100819
• Publication Date: 2022-11-16T05:02:28Z
• Authors: Anthony R. Soltis; Nicholas W. Bateman; Jianfang Liu; Trinh Nguyen; Teri J. Franks; Xijun Zhang; Clifton L. Dalgard; Coralie Viollet; Stella Somiari; Chunhua Yan; Karen Zeman; William J. Skinner; Jerry S.H. Lee; Harvey B. Pollard; Clesson Turner; Emanuel F. Petricoin; Daoud Meerzaman; Thomas P. Conrads; Hai Hu; Rebecca Blackwell; Gauthaman Sukumar; Dagmar Bacikova; Camille Alba; Elisa McGrath; Sraavya Polisetti; Meila Tuck; Alden Chiu; Gabe Peterson; Caroline Larson; Leonid Kvecher; Brenda Deyarmin; Jennifer Kane; Katie Miller; Kelly A. Conrads; Brian L. Hood; Sasha C. Makohon-...; Tamara S. Abulez; Elisa Baldelli; Mariaelena Pierobon; Qing-rong Chen; Henry Rodriguez; Sean E. Hanlon; Anthony R. Soltis; Nicholas W. Bateman; Jianfang Liu; Trinh Nguyen; Teri J. Franks; Xijun Zhang; Clifton L. Dalgard; Coralie Viollet; Stella Somiari; Chunhua Yan; Karen Zeman; William J. Skinner; Jerry S.H. Lee; Harvey B. Pollard; Clesson Turner; Emanuel F. Petricoin; Daoud Meerzaman; Thomas P. Conrads; Hai Hu; Craig D. Shriver; Christopher A. Mo...; Robert F. Browning; Matthew D. Wilkerson; Craig D. Shriver; Christopher A. Mo...; Robert F. Browning; Matthew D. Wilkerson
• Keywords: Tumor Heterogeneity

We present a deep proteogenomic profiling study of 87 lung adenocarcinoma (LUAD) tumors from the United States, integrating whole-genome sequencing, transcriptome proteomics and phosphoproteomics by mass spectrometry, reverse-phase protein arrays. identify three subtypes somatic genome signature analysis, including transition-high subtype enriched with never smokers, transversion-high current structurally altered former TP53 alterations, genome-wide structural alterations. show that within-tumor correlations RNA expression associate tumor purity immune cell profiles. detect independently validate signatures predict patient survival. Additionally, among co-measured genes, we found is more often associated survival than RNA. Finally, integrative analysis characterizes divergent mutations, proteomic regulatory networks, therapeutic vulnerabilities. This characterization provides foundation for molecularly informed medicine in LUAD.