Sistema de Salut de Catalunya
Institut Català de la Salut
[Nassar AH] Department of Medicine (Medical Oncology), Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA. [Kim C] Division of Hematology and Oncology, Georgetown Cancer Institute, Washington, DC, USA. [Adeyelu T] Caris Life Sciences, Phoenix, AZ, USA. [Bou Farhat E] Division of Pulmonary Medicine, Brigham and Women’s Hospital, Boston, MA, USA. [Abushukair H] Division of Medical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Department of Oncology Science, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. [Rakaee M] Division of Pulmonary Medicine, Brigham and Women’s Hospital, Boston, MA, USA. Department of Cancer Genetics, Oslo University Hospital, Oslo, Norway. [Rocha P] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-11-03T13:46:57Z
2025-11-03T13:46:57Z
2025-08-19
Integrated molecular; Pulmonary large cell neuroendocrine carcinoma
Caracterització molecular; Carcinoma neuroendocrí pulmonar de cèl·lules grans
Caracterización molecular; Carcinoma neuroendocrino pulmonar de células grandes
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung tumor marked by significant molecular heterogeneity. In a study of 590 patients across two independent cohorts, we observe comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events. Genomic analysis identifies distinct non-small cell lung cancer-like (NSCLC-like, KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations) LCNEC subtypes, with 80% aligning with SCLC transcriptional profiles. Serial sampling reveals stable mutational but shifting transcriptomic landscapes over time. Here we show, elevated FGL-1 (a LAG-3 ligand) and SPINK1 expression in NSCLC-like LCNECs, and higher levels of DLL3 in SCLC-like LCNECs. Immunofluorescence confirms FGL-1 expression in NSCLC-like LCNECs, and H&E slide analyses indicates fewer tumor-infiltrating lymphocytes in LCNECs versus other lung cancers. These findings highlight LCNEC's distinct immunogenomic profile, supporting future investigations into LAG-3, SPINK1, and DLL3-targeted therapies.
Article
Published version
English
Anomalies cromosòmiques; Pulmons - Càncer - Tractament; Tumors neuroendocrins; DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors::Carcinoma, Neuroendocrine; DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos::carcinoma neuroendocrino; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
Nature Portfolio
Nature Communications;16
https://doi.org/10.1038/s41467-025-63091-0
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
Articles científics - HVH [3396]
