Molecular Characterization and Prognostication of Large Cell Neuroendocrine Carcinoma and Large Cell Carcinoma

• Published in: Frontiers in oncology Vol. 11; p. 664397
• Main Authors: Chen, Ying, Cui, Xiaoying, Wang, Di, Xia, Guojie, Xing, Minyan, Cheng, Lei, Sheng, Liming, Du, Xianghui
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 14.01.2022
• Subjects: BRAF; KEAP1; large cell carcinoma; Oncology; RB1; SMARCA4; RB1; KEAP1; BRAF; large cell carcinoma; SMARCA4
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.664397

Large cell neuroendocrine carcinoma (LCNEC) and classic large cell carcinoma (LCC) are two distinct entities with different histological and biological characteristics. However, the mutational profiles and the clinical behavior of the two subtypes of lung cancer remain to be explored. Pathological diagnoses of all screened patients were finally confirmed by three or four experienced pathologists. Patients with uncertain pathological diagnoses were excluded. Finally, we genetically profiled ten patients with LCNEC and seven with LCC. ALL patients were subjected to next-generation sequencing (NGS) test, which included nine patients sequenced with a 139-gene panel and eight patients with a 425-gene panel. Including only intersected mutations from these two panels, survival analysis was further conducted. Both LCNEC and LCC showed high prevalence in male patients, with no clear association with smoking history. Potential targetable mutations in and were detected in the study cohort. However, LCNEC and LCC showed distinct mutational profiles with an enrichment of / co-mutations in a subset of LCNEC patients. and mutations were exclusively found in LCC patients, and , , and mutations were only detected in LCNEC. LCC patients in the cohort had shorter survival compared to LCNEC patients (p=0.006). Survival analysis revealed an association between mutations and poor outcome in the study cohort and in the LCC subset. Mutations in were associated with a trend of increased survival in the study cohort, as well as in the LCNEC subset. Finally, mutations were associated with poor outcome in the LCNEC cohort. LCC and LCNEC were both heterogeneous diseases with limited treatment options. Our study identified potential targetable mutations and prognostic biomarkers that might provide more therapeutic options and improve individualized patient care.