{ "abstract": "Integrated assessment of tumour genomics and immune biomarkers may improve prognostic stratification in non-small cell lung cancer (NSCLC). We examined the distribution and prognostic relevance of somatic pathogenic/likely pathogenic variants (PVs), somatic copy-number alterations (SCNAs), programmed death-ligand 1 (PD-L1) expression and tumour-infiltrating lymphocytes (TILs) in a multicentre cohort. This retrospective, multicentre study included 367 unselected patients with histologically confirmed NSCLC treated at 19 centres in Greece between 2000 and 2020. Targeted next-generation sequencing (NGS) was performed in 267 tumours; PD-L1 tumour proportion score (TPS) and haematoxylin and eosin (H&E)-based TIL density were evaluated in 298 and 352 tumours, respectively. Overall survival (OS) was assessed using Kaplan-Meier and multivariable Cox regression analyses. TP53 (53.6%) and KRAS (16.5%) were the most frequently detected genes with PVs; SCNAs were identified in 22.5% of sequenced tumours and were more frequent in squamous than non-squamous histology. In multivariable analysis (254 complete cases), TIL density ≥10% (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.52-0.99; p = 0.042) and ≥2 mutated genes (HR 1.44, 95% CI 1.08-1.92; p = 0.014) were independently associated with OS. PIK3CA-containing copy-number gains were significantly enriched in squamous tumours with low TIL density (p = 0.024), while FGFR1-containing copy-number gains showed a similar but non-significant trend (p = 0.088). In the present retrospective study, co-mutation burden and TIL density provided complementary prognostic information beyond clinicopathological variables in NSCLC. The association between selected copy-number gains and an immune-poor squamous phenotype warrants prospective validation.", "abstract_shown": true, "affiliations": [ "Department of Medical Oncology, Papageorgiou Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, 56403 Thessaloniki, Greece.", "Medicover Genetics, 2409 Nicosia, Cyprus.", "Department of Pathology, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.", "Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, 54124 Thessaloniki, Greece.", "2nd Department of Pathology, Attikon University Hospital, National and Kapodistrian University of Athens, 12461 Athens, Greece.", "Lung Cancer Oncology Unit, Pulmonary Department, G. Papanikolaou Hospital, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece.", "Department of Pathology, Ioannina University Hospital, 45500 Ioannina, Greece.", "Department of Medical Oncology, St Luke's Clinic, Panorama, 55236 Thessaloniki, Greece.", "School of Medicine, European University Cyprus, 2404 Engomi, Cyprus.", "Laboratory of Histology and Embryology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.", "Institute of Applied Biosciences, Centre for Research and Technology Hellas, 60361 Thessaloniki, Greece.", "Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, Greece.", "Fourth Oncology Department and Comprehensive Clinical Trials Center, Metropolitan Hospital, 18547 Athens, Greece.", "Department of Medical Oncology, Medical School, University of Ioannina, 45500 Ioannina, Greece.", "First Department of Medical Oncology, Metropolitan Hospital, 18547 Athens, Greece.", "Oncology Section, Second Department of Internal Medicine, Hippokratio Hospital, 11527 Athens, Greece.", "Second Department of Medical Oncology, Hygeia Hospital, 15123 Athens, Greece.", "Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.", "Department of Respiratory Medicine, \"G. Papanikolaou\" General Hospital of Thessaloniki, 57010 Thessaloniki, Greece.", "Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece." ], "article_type": "research article", "arxiv": null, "author_total": 26, "authors": [ { "affs": [ 0 ], "name": "Konstantinos Efthymiadis" }, { "affs": [ 1 ], "name": "Chrysa Soteriou", "orcid": "0000-0002-2808-1215" }, { "affs": [ 2 ], "name": "Vassiliki Kotoula" }, { "affs": [ 3 ], "name": "Kyriaki Papadopoulou", "orcid": "0000-0003-0389-4209" }, { "affs": [ 4 ], "name": "Abraham Pouliakis", "orcid": "0000-0002-0074-3619" }, { "affs": [ 5 ], "name": "Sofia Lampaki" }, { "affs": [ 6 ], "name": "Anna Goussia" }, { "affs": [ 7, 8 ], "name": "Elena Fountzilas" }, { "affs": [ 9 ], "name": "Soultana Meditskou" }, { "affs": [ 3 ], "name": "Mattheos Bobos", "orcid": "0000-0001-5662-9201" }, { "affs": [ 10 ], "name": "Konstantinos Kyritsis", "orcid": "0000-0001-8035-341X" }, { "affs": [ 1 ], "name": "Christos Lemesios" }, { "affs": [ 11 ], "name": "Epaminontas Samantas" }, { "affs": [ 12 ], "name": "Evangelos Sarris" }, { "affs": [ 13 ], "name": "George Pentheroudakis" }, { "affs": [ 14 ], "name": "Dimitrios Bafaloukos" }, { "affs": [ 15 ], "name": "Dimitrios Pectasides" }, { "affs": [ 16 ], "name": "Paris A Kosmidis", "orcid": "0009-0003-1478-0087" }, { "affs": [ 17 ], "name": "Flora Zagouri", "orcid": "0000-0001-7153-6556" }, { "affs": [ 18 ], "name": "Dionysis Spyratos" }, { "affs": [ 0 ], "name": "Eleni Timotheadou", "orcid": "0000-0003-2545-8926" }, { "affs": [ 2 ], "name": "Prodromos Hytiroglou", "orcid": "0000-0003-3412-2914" }, { "affs": [ 1 ], "name": "Alexia Eliades", "orcid": "0000-0001-8459-7163" }, { "affs": [ 1 ], "name": "George Koumbaris" }, { "affs": [ 3, 19 ], "name": "George Fountzilas", "orcid": "0000-0001-8045-2186" }, { "affs": [ 12 ], "name": "Helena Linardou" } ], "bibtex": "https://research.draconitic.com/paper/fsz054y658wve.bib", "cited_by": 0, "doi": "10.3390/ijms27198724", "fulltext_url": "https://europepmc.org/articles/PMC13665066", "id": "fsz054y658wve", "issns": [ "1422-0067" ], "landing_url": "https://europepmc.org/article/MED/42883968", "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": "W7214700889", "pdf_url": "https://europepmc.org/articles/PMC13665066?pdf=render", "pmcid": "PMC13665066", "pmid": "42883968", "published": "2026-09-29", "publisher": null, "ris": "https://research.draconitic.com/paper/fsz054y658wve.ris", "sources": [ { "first_seen": "2026-10-30T12:19:16Z", "native_id": "MED:42883968", "source": "europepmc", "url": "https://europepmc.org/article/MED/42883968" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2740|Lung Cancer Treatments and Mutations", "subfield": "general" } ], "title": "Integrated Molecular, Clinicopathological and Immune Profiling of Non-Small Cell Lung Cancer: The MONREPOS Hellenic Cooperative Oncology Group (HeCOG) Study (HE_2TR/13).", "title_text": "Integrated Molecular, Clinicopathological and Immune Profiling of Non-Small Cell Lung Cancer: The MONREPOS Hellenic Cooperative Oncology Group (HeCOG) Study (HE_2TR/13).", "type": "peer-reviewed", "updated_at": "2026-10-30T12:19:16Z", "url": "https://research.draconitic.com/paper/fsz054y658wve", "venue": "International journal of molecular sciences", "versions": [] }