dc.contributor
Institut Català de la Salut
dc.contributor
[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
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Nassar, Amin
dc.contributor.author
Kim, Chul
dc.contributor.author
Adeyelu, Tolulope
dc.contributor.author
Bou Farhat, Elias
dc.contributor.author
Abushukair, Hassan
dc.contributor.author
Rakaee, Mehrdad
dc.contributor.author
Rocha, Pedro
dc.date.accessioned
2025-11-04T17:45:47Z
dc.date.available
2025-11-04T17:45:47Z
dc.date.issued
2025-11-03T13:46:57Z
dc.date.issued
2025-11-03T13:46:57Z
dc.date.issued
2025-08-19
dc.identifier
Nassar AH, Kim C, Adeyelu T, Bou Farhat E, Abushukair H, Rakaee M, et al. Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma. Nat Commun. 2025 Aug 19;16:7717.
dc.identifier
http://hdl.handle.net/11351/14003
dc.identifier
10.1038/s41467-025-63091-0
dc.identifier
001554401700023
dc.identifier.uri
http://hdl.handle.net/11351/14003
dc.description.abstract
Integrated molecular; Pulmonary large cell neuroendocrine carcinoma
dc.description.abstract
Caracterització molecular; Carcinoma neuroendocrí pulmonar de cèl·lules grans
dc.description.abstract
Caracterización molecular; Carcinoma neuroendocrino pulmonar de células grandes
dc.description.abstract
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.
dc.format
application/pdf
dc.publisher
Nature Portfolio
dc.relation
Nature Communications;16
dc.relation
https://doi.org/10.1038/s41467-025-63091-0
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Anomalies cromosòmiques
dc.subject
Pulmons - Càncer - Tractament
dc.subject
Tumors neuroendocrins
dc.subject
DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors::Carcinoma, Neuroendocrine
dc.subject
DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
dc.subject
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos::carcinoma neuroendocrino
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
dc.title
Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
