{ "abstract": "Objectives\n\nPrecision medicine has improved outcomes in advanced lung cancer, but its implementation remains limited. The prospective LANTERN project (NCT05802771) involves comprehensive clinical and multi-omics data collection. Here, we report preliminary genomic findings, focusing on the prognostic impact of gene mutations, pairwise co-mutational patterns, and their stage-specific association with PD-L1 analysis on patients speciments.Methods\n\nThis prospective, multicenter observational study enrolled 271 consecutive patients between March 2023 and December 2024, including 137 with stage I-III and 134 with stage IV disease. Comprehensive genomic profiling was performed using the TruSight Oncology 500 High Throughput assay to assess single nucleotide variants, insertions/deletions, copy number alterations, tumor mutational burden and microsatellite instability. The prognostic role of mutations and co-mutations was evaluated, together with associations between genomic alterations and PD-L1 expression.Results\n\nAt least one Tier I-II alteration was identified in 84% of patients. TP53 (39%), KRAS (27%), EGFR (15%), and STK11 (11%) were the most frequently altered genes. Several co-mutations were associated with worse overall survival, including TP53/STK11, STK11/LRP1B, STK11/RB1 and RB1/LRP1B, and with reduced disease-free survival, particularly TP53/KRAS, TP53/STK11, KRAS/STK11 and STK11/LRP1B. In advanced disease, STK11 and KEAP1 mutations were associated with low PD-L1 expression, whereas PIK3CA, PTEN and ARID1A mutations correlated with higher PD-L1 expression in early-stage tumors.Conclusions\n\nComprehensive genomic profiling reveals substantial molecular heterogeneity across lung cancer stages and identifies co-mutational patterns with prognostic and immune-related relevance, supporting broader molecular testing at diagnosis.", "abstract_shown": true, "affiliations": [ "Thoracic Surgery Unit, A. Gemelli University Hospital Foundation IRCCS, 00168 Rome, Italy.", "Departmental Unit of Molecular and Genomic Diagnostics, Genomics Research Core Facility, Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.", "Clinical Chemistry, Biochemistry and Molecular Biology Operations (UOC), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.", "OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany.", "Institute of Pathology, A. Gemelli University Hospital Foundation IRCCS, 00168 Rome, Italy.", "Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and Universit Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307 Dresden, Germany.", "ELKH-DE Public Health Research Group, Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4028 Debrecen, Hungary.", "Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau (IR-HSCSP), 08041 Barcelona, Spain.", "School of Medicine, Turkey and Koç University Research Center for Translational Medicine (KUTTAM), Koç University, Sariyer, 34450 Istanbul, Turkey.", "Interventional Pulmonology Unit, A. Gemelli University Hospital Foundation IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy.", "Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario \"A. Gemelli\" IRCCS, 00168 Rome, Italy.", "Istituto di Radiologia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.", "Radiomics Core Research Facility, Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.", "Medical Oncology, Comprehensive Cancer Center, IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Largo Francesco Vito, 1, 00168 Rome, Italy.", "Medical Oncology Unit, Ospedale Isola Tiberina-Gemelli Isola, 00168 Rome, Italy." ], "article_type": "research article", "arxiv": null, "author_total": 20, "authors": [ { "affs": [ 0 ], "name": "Carolina Sassorossi", "orcid": "0000-0003-4654-1577" }, { "affs": [ 1, 2 ], "name": "Elisa De Paolis" }, { "affs": [ 0, 1 ], "name": "Jessica Evangelista" }, { "affs": [ 3 ], "name": "Davide Dalfovo" }, { "affs": [ 4 ], "name": "Alessandra Cancellieri" }, { "affs": [ 1 ], "name": "Ilenia Carriero" }, { "affs": [ 0 ], "name": "Annalisa Campanella" }, { "affs": [ 4, 5 ], "name": "Esther G C Troost" }, { "affs": [ 4, 5 ], "name": "Steffen Löck", "orcid": "0000-0002-7017-3738" }, { "affs": [ 6 ], "name": "Róza Ádány", "orcid": "0000-0002-9679-6669" }, { "affs": [ 7 ], "name": "Núria Farré", "orcid": "0000-0002-3604-3956" }, { "affs": [ 8 ], "name": "Ece Öztürk", "orcid": "0000-0001-8635-0279" }, { "affs": [ 9 ], "name": "Rocco Trisolini", "orcid": "0000-0002-1067-4696" }, { "affs": [ 10, 11, 12 ], "name": "Luca Boldrini", "orcid": "0000-0002-5631-1575" }, { "affs": [ 13 ], "name": "Alessio Stefani", "orcid": "0000-0002-5816-4484" }, { "affs": [ 2 ], "name": "Andrea Urbani" }, { "affs": [ 13, 14 ], "name": "Emilio Bria" }, { "affs": [ 0 ], "name": "Stefano Margaritora" }, { "affs": [ 2 ], "name": "Angelo Minucci", "orcid": "0000-0002-0833-4334" }, { "affs": [ 0 ], "name": "Filippo Lococo" } ], "bibtex": "https://research.draconitic.com/paper/eyq80c4ey6729.bib", "cited_by": 0, "doi": "10.3390/genes17101233", "fulltext_url": "https://europepmc.org/articles/PMC13704353", "id": "eyq80c4ey6729", "issns": [ "2073-4425" ], "landing_url": "https://europepmc.org/article/MED/42938349", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2740|Lung Cancer Treatments and Mutations" ] ], "openalex": "W7220387694", "pdf_url": "https://europepmc.org/articles/PMC13704353?pdf=render", "pmcid": "PMC13704353", "pmid": "42938349", "published": "2026-10-05", "publisher": null, "ris": "https://research.draconitic.com/paper/eyq80c4ey6729.ris", "sources": [ { "first_seen": "2026-10-30T12:22:24Z", "native_id": "MED:42938349", "source": "europepmc", "url": "https://europepmc.org/article/MED/42938349" } ], "subjects": [ { "field": "biology", "origin": "journal-openalex:1311|Genomics and Rare Diseases", "subfield": "genetics-genomics" } ], "title": "Clinical Utility of Broad-Panel Profiling in Non-Small Cell Lung Cancer: Pairwise Co-Mutational Gene Patterns and PD-L1 Associations Define Stage-Specific Prognosis.", "title_text": "Clinical Utility of Broad-Panel Profiling in Non-Small Cell Lung Cancer: Pairwise Co-Mutational Gene Patterns and PD-L1 Associations Define Stage-Specific Prognosis.", "type": "peer-reviewed", "updated_at": "2026-10-30T12:22:24Z", "url": "https://research.draconitic.com/paper/eyq80c4ey6729", "venue": "Genes", "versions": [] }