Human · observationalMechanismMixed resultsLimited evidenceTier 3 · early humann = 590
Nature communications · Aug 2025 · cohort study (two independent clinical/genomic cohorts)
pulmonary large cell neuroendocrine carcinoma (LCNEC)small cell lung cancer (SCLC)non-small cell lung cancer (NSCLC)
The authors analyzed clinical and molecular data from 590 patients with pulmonary large cell neuroendocrine carcinoma across two cohorts. They identified two genomic subtypes (NSCLC-like with KEAP1/KRAS/STK11 mutations and SCLC-like with RB1/TP53 mutations) and report that 80% of tumors aligned with SCLC transcriptional profiles. The study found elevated FGL-1 and SPINK1 expression in NSCLC-like LCNECs and higher DLL3 in SCLC-like LCNECs, and noted fewer tumor-infiltrating lymphocytes in LCNEC compared with other lung cancers. Overall survival was comparable across chemotherapy, chemoimmunotherapy, and immunotherapy in this cohort.
Reported effect: proportion aligning with SCLC transcriptional profiles 80%, n=590
Key findings
- Study cohort: 590 patients across two independent cohorts.
- Comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events.
- Genomic analysis identified two LCNEC subtypes: NSCLC-like (KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations).
- 80% of LCNEC tumors aligned with SCLC transcriptional profiles.
- Serial sampling showed stable mutational landscapes but shifting transcriptomic profiles over time.
- Elevated FGL-1 (a LAG-3 ligand) and SPINK1 expression were observed in NSCLC-like LCNECs; DLL3 levels were higher in SCLC-like LCNECs.
- Immunofluorescence confirmed FGL-1 expression in NSCLC-like LCNECs.
- H&E analyses indicated fewer tumor-infiltrating lymphocytes in LCNECs versus other lung cancers.
- Authors suggest these immunogenomic features support future investigation of LAG-3, SPINK1, and DLL3-targeted approaches.
Limitations: Observational cohort design — no randomized comparison of treatments reported in the abstract.; Abstract provides no quantitative survival or subgroup outcome measures (no effect sizes or statistical details reported).; Molecular associations (expression of FGL-1, SPINK1, DLL3) are descriptive and do not demonstrate therapeutic efficacy.; Functional or clinical validation of proposed targets is not presented in the abstract.; H&E-based assessment of tumor-infiltrating lymphocytes is a histologic surrogate and may lack detailed immunophenotyping..
Identifies immunogenomic subtypes and candidate targets (FGL-1/LAG-3, SPINK1, DLL3) in LCNEC that may guide future therapeutic investigations.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 79
Translational oncology · May 2022
pulmonary large cell neuroendocrine carcinoma (LCNEC)
The authors performed immunohistochemistry on tissue microarrays from 79 resected LCNEC cases to measure ALDH1A1, E-cadherin and N-cadherin and to correlate expression with clinicopathologic features and survival. ALDH1A1 was positive in 75.9% of tumors and was positively correlated with E-cadherin but not with N-cadherin. Patients with ALDH1A1 expression had longer median disease-free survival (52 vs 12 months) and better overall survival, and multivariate analysis identified ALDH1A1 as an independent favorable prognostic factor.
Reported effects: ALDH1A1 positive expression 75.9%, n=79 · Spearman correlation with E-cadherin 0.229, p=0.007 · +4 more
Key findings
- ALDH1A1 was positively expressed in 75.9% (60/79 cases) of LCNEC patients.
- No significant difference in clinicopathological variables was observed between ALDH1A1-negative and ALDH1A1-positive groups.
- ALDH1A1 expression was positively correlated with E-cadherin (Spearman's rho = 0.229, p-value = 0.007) but not with N-cadherin.
- Patients with ALDH1A1 expression had significantly longer disease-free survival (median DFS: 52 vs 12 months, p = 0.028) and overall survival (median OS: not reached; p = 0.027) than ALDH1A1-negative patients.
- Multivariate analysis showed ALDH1A1 was an independent favorable prognostic factor for DFS (p = 0.032, HR: 0.438, 95% CI: 0.206-0.932) and OS (p = 0.025, HR: 0.279, 95% CI: 0.091-0.852).
Limitations: Observational IHC study on archived resected samples — correlation does not prove causation.; Moderate sample size (n=79) which may limit statistical power.; No external validation cohort reported.; No functional or mechanistic experiments to explain the observed associations (authors note mechanism needs further study)..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text