Integrated Molecular, Clinicopathological and Immune Profiling of Non-Small Cell Lung Cancer: The MONREPOS Hellenic Cooperative Oncology Group (HeCOG) Study (HE_2TR/13).

@article{efthymiadis2026integrated,
  title = {{Integrated Molecular, Clinicopathological and Immune Profiling of Non-Small Cell Lung Cancer: The MONREPOS Hellenic Cooperative Oncology Group (HeCOG) Study (HE_2TR/13).}},
  author = {Konstantinos Efthymiadis and Chrysa Soteriou and Vassiliki Kotoula and Kyriaki Papadopoulou and Abraham Pouliakis and Sofia Lampaki and Anna Goussia and Elena Fountzilas and Soultana Meditskou and Mattheos Bobos and Konstantinos Kyritsis and Christos Lemesios and Epaminontas Samantas and Evangelos Sarris and George Pentheroudakis and Dimitrios Bafaloukos and Dimitrios Pectasides and Paris A Kosmidis and Flora Zagouri and Dionysis Spyratos and Eleni Timotheadou and Prodromos Hytiroglou and Alexia Eliades and George Koumbaris and George Fountzilas and Helena Linardou},
  journal = {International journal of molecular sciences},
  year = {2026},
  month = sep,
  doi = {10.3390/ijms27198724},
  url = {https://europepmc.org/article/MED/42883968},
  note = {CC BY},
}

TY  - JOUR
TI  - Integrated Molecular, Clinicopathological and Immune Profiling of Non-Small Cell Lung Cancer: The MONREPOS Hellenic Cooperative Oncology Group (HeCOG) Study (HE_2TR/13).
AU  - Konstantinos Efthymiadis
AU  - Chrysa Soteriou
AU  - Vassiliki Kotoula
AU  - Kyriaki Papadopoulou
AU  - Abraham Pouliakis
AU  - Sofia Lampaki
AU  - Anna Goussia
AU  - Elena Fountzilas
AU  - Soultana Meditskou
AU  - Mattheos Bobos
AU  - Konstantinos Kyritsis
AU  - Christos Lemesios
AU  - Epaminontas Samantas
AU  - Evangelos Sarris
AU  - George Pentheroudakis
AU  - Dimitrios Bafaloukos
AU  - Dimitrios Pectasides
AU  - Paris A Kosmidis
AU  - Flora Zagouri
AU  - Dionysis Spyratos
AU  - Eleni Timotheadou
AU  - Prodromos Hytiroglou
AU  - Alexia Eliades
AU  - George Koumbaris
AU  - George Fountzilas
AU  - Helena Linardou
PY  - 2026
DA  - 2026/09/29
JO  - International journal of molecular sciences
DO  - 10.3390/ijms27198724
UR  - https://europepmc.org/article/MED/42883968
AB  - 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.
SN  - 1422-0067
ER  -