Citations 1
Integrated Molecular and Clinical Characterization of Pulmonary Large Cell Neuroendocrine Carcinoma
Chiang, Anne C. , Nassar, Amin H. , Kim, Chul , Farhat, Elias Bou , Matteson, Kelsey, Lau, Shun‐Fat , Gallegos, Jesús Antonio Ocejo , Ardeshir‐Larijani, Fatemeh , Leal, Ticiana, Alam, Sumaye, Gray, Jhanelle E. , Hicks, J. Kevin , Kaldas, David , Baena, Javier, Berjaga, María Zurera, Grohé, Christian , Leuders, Heike, Mingo, Emanuele Claudio , Pancirer, Danny, Cheung, Justin M., Lin, Jessica, Watson, Alexander, Camidge, D. Ross , Parikh, Kaushal , Aggarwal, Vanya , Ahmed, Murtaza, Zhang, Jun , Nagasaka, Misako , Awosika, Nichola, Alhamad, Khaled, Zaman, Unaiza, Gupta, Divya , Lau, Chelsea, Khan, Hina, Liauw, Justin , Brown, Tyiesha , Mosteiro, Miguel , Lopes, Gilberto , Patrick, C. , Young, Lauren K. , Aljumaily, Raid, Mirza, Haris , TAKEBE, Y., Baena, Javier , Nassar, Amin H. , Ocejo Gallegos, Jesus Antonio , Bou Farhat, Elias , Espinar, Javier Baena , Adeyelu, Tolulope Tosin , Abushukair, Hassan , Rakaee, Mehrdad , Takabe, Yamato J. , Ramalingam, Suresh S. , Alam, Sumaiya, Nana, Frank Aboubakar , Citarella, Fabrizio , Cortellini, Alessio , Das, Millie , Ellis-Caleo, Timothy John , Linehan, William Marston , Sridhar, Arthi , Crowley, Fionnuala , Marron, Thomas , Sankar, K. Nathan , Kawtharany, Hassan , Owen, Dwight H , Li, Mingjia , Pinato, David J. , Puri, Sonam , Velázquez, Ana I. , Moliner, Laura , Rocha, Pedro , Evans, Mark G. , Vanderwalde, Ari M. , Elliott, Andrew , Nieva, Jorgé , Patrick, C. , Borghaei, Hossein , Lee, Matthew , Kwiatkowski, David J. , Herbst, Roy S. , Flavell, Richard A. , Naqash, Abdul Rafeh
No container title available | May 16, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
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 observed comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events. Genomic analysis identified distinct NSCLC-like (KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations) LCNEC subtypes, with 80% aligning with SCLC transcriptional profiles. Serial sampling revealed stable mutational but shifting transcriptomic landscapes over time. NSCLC-like LCNECs showed elevated FGL-1 (a LAG-3 ligand) and SPINK1 expression, while SCLC-like subtypes expressed higher levels of DLL3. Immunofluorescence confirmed FGL-1 in NSCLC-like LCNECs, and H&E slide analyses indicated 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.