Nature communications · 2025

Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma.

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Nassar Amin H, Kim Chul, Adeyelu Tolulope, Bou Farhat Elias, Abushukair Hassan, Rakaee Mehrdad, Matteson Kelsey, Lau Shun-Fat, Takabe Yamato, Ocejo Antonio, Ardeshir-Larijani Fatemeh, Leal Ticiana, Ramalingam Suresh, Alam Sumaiya, Gray Jhanelle E, Hicks James, Kaldas David, Baena Javier, Berjaga Maria Zurera, Nana Frank Aboubakar, Grohe Christian, Leuders Heike, Citarella Fabrizio, Cortellini Alessio, Mingo Emanuele Claudio, Pancirer Danny, Das Millie, Ellis-Caleo Timothy John, Cheung Justin M, Lin Jessica J, Watson Alexander S, Camidge D Ross, Sridhar Arthi, Parikh Kaushal, Crowley Fionnuala, Marron Thomas U, Aggarwal Vanya, Ahmed Murtaza, Sankar Kamya, Kawtharany Hassan, Zhang Jun, Owen Dwight H, Li Mingjia, Nagasaka Misako, Pinato David J, Awosika Nichola, Alhamad Khaled, Puri Sonam, Zaman Unaiza, Gupta Divya M, Lau Chelsea, Khan Hina, Liauw Justin, Velazquez Ana I, Brown Tyiesha, Moliner Laura, Mosteiro Miguel, Rocha Pedro, Evans Mark, Vanderwalde Ari, Elliott Andrew, Nieva Jorge, Lopes Gilberto, Ma Patrick C, Borghaei Hossein, Lee Matthew, Young Lauren, Aljumaily Raid, Mirza Haris, Kwiatkowski David J, Herbst Roy S, Flavell Richard A, Naqash Abdul Rafeh, Chiang Anne C

Аннотация

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.

Предметные рубрики MeSH

Humans Lung Neoplasms Carcinoma, Neuroendocrine Male Female Carcinoma, Large Cell Membrane Proteins Mutation Middle Aged Trypsin Inhibitor, Kazal Pancreatic Intracellular Signaling Peptides and Proteins Aged Carcinoma, Non-Small-Cell Lung Gene Expression Regulation, Neoplastic Lymphocytes, Tumor-Infiltrating Kelch-Like ECH-Associated Protein 1 Biomarkers, Tumor

Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma.

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Аннотация

Предметные рубрики MeSH