{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:18Z","timestamp":1792789638284,"version":"4.5.0"},"reference-count":81,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hellenic Society of Medical Oncology","award":["6958\/22-12-2017"],"award-info":[{"award-number":["6958\/22-12-2017"]}],"id":[{"id":"https:\/\/ror.org\/02ar9bs92","id-type":"ROR","asserted-by":"crossref"}]},{"award":["6958\/22-12-2017"],"award-info":[{"award-number":["6958\/22-12-2017"]}],"id":[{"id":"https:\/\/ror.org\/02ar9bs92","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hellenic Cooperative Oncology Group","award":["HE_2TR\/13"],"award-info":[{"award-number":["HE_2TR\/13"]}],"id":[{"id":"https:\/\/ror.org\/02bxsvn11","id-type":"ROR","asserted-by":"crossref"}]},{"award":["HE_2TR\/13"],"award-info":[{"award-number":["HE_2TR\/13"]}],"id":[{"id":"https:\/\/ror.org\/02bxsvn11","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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&amp;E)-based TIL density were evaluated in 298 and 352 tumours, respectively. Overall survival (OS) was assessed using Kaplan\u2013Meier 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 \u226510% (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.52\u20130.99; p = 0.042) and \u22652 mutated genes (HR 1.44, 95% CI 1.08\u20131.92; 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.<\/jats:p>","DOI":"10.3390\/ijms27198724","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:33:12Z","timestamp":1790699592000},"page":"8724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Molecular, Clinicopathological and Immune Profiling of Non-Small Cell Lung Cancer: The MONREPOS Hellenic Cooperative Oncology Group (HeCOG) Study (HE_2TR\/13)"],"prefix":"10.3390","volume":"27","author":[{"given":"Konstantinos","family":"Efthymiadis","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Papageorgiou Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2808-1215","authenticated-orcid":false,"given":"Chrysa","family":"Soteriou","sequence":"additional","affiliation":[{"name":"Medicover Genetics, 2409 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki","family":"Kotoula","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-4209","authenticated-orcid":false,"given":"Kyriaki","family":"Papadopoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0074-3619","authenticated-orcid":false,"given":"Abraham","family":"Pouliakis","sequence":"additional","affiliation":[{"name":"2nd Department of Pathology, Attikon University Hospital, National and Kapodistrian University of Athens, 12461 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Lampaki","sequence":"additional","affiliation":[{"name":"Lung Cancer Oncology Unit, Pulmonary Department, G. Papanikolaou Hospital, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Goussia","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ioannina University Hospital, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Fountzilas","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, St Luke\u2019s Clinic, Panorama, 55236 Thessaloniki, Greece"},{"name":"School of Medicine, European University Cyprus, 2404 Engomi, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soultana","family":"Meditskou","sequence":"additional","affiliation":[{"name":"Laboratory of Histology and Embryology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5662-9201","authenticated-orcid":false,"given":"Mattheos","family":"Bobos","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8035-341X","authenticated-orcid":false,"given":"Konstantinos","family":"Kyritsis","sequence":"additional","affiliation":[{"name":"Institute of Applied Biosciences, Centre for Research and Technology Hellas, 60361 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Lemesios","sequence":"additional","affiliation":[{"name":"Medicover Genetics, 2409 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Epaminontas","family":"Samantas","sequence":"additional","affiliation":[{"name":"Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Sarris","sequence":"additional","affiliation":[{"name":"Fourth Oncology Department and Comprehensive Clinical Trials Center, Metropolitan Hospital, 18547 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Pentheroudakis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Medical School, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Bafaloukos","sequence":"additional","affiliation":[{"name":"First Department of Medical Oncology, Metropolitan Hospital, 18547 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Pectasides","sequence":"additional","affiliation":[{"name":"Oncology Section, Second Department of Internal Medicine, Hippokratio Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1478-0087","authenticated-orcid":false,"given":"Paris A.","family":"Kosmidis","sequence":"additional","affiliation":[{"name":"Second Department of Medical Oncology, Hygeia Hospital, 15123 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-6556","authenticated-orcid":false,"given":"Flora","family":"Zagouri","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dionysis","family":"Spyratos","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, \u201cG. Papanikolaou\u201d General Hospital of Thessaloniki, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2545-8926","authenticated-orcid":false,"given":"Eleni","family":"Timotheadou","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Papageorgiou Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3412-2914","authenticated-orcid":false,"given":"Prodromos","family":"Hytiroglou","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8459-7163","authenticated-orcid":false,"given":"Alexia","family":"Eliades","sequence":"additional","affiliation":[{"name":"Medicover Genetics, 2409 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Koumbaris","sequence":"additional","affiliation":[{"name":"Medicover Genetics, 2409 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8045-2186","authenticated-orcid":false,"given":"George","family":"Fountzilas","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, 54124 Thessaloniki, Greece"},{"name":"Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Linardou","sequence":"additional","affiliation":[{"name":"Fourth Oncology Department and Comprehensive Clinical Trials Center, Metropolitan Hospital, 18547 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. 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