ArticleBiological procedures online2026
Prognostic Significance and Immune Landscape of Neuroendocrine Differentiation-Related Genes in Non-Small Cell Lung Cancer.
Article in Biological procedures online, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundImmunotherapy resistance represents a current research hotspot. Previous studies found that neuroendocrine differentiation (NED) might significantly contribute to the initiation and development of non-small cell lung cancer (NSCLC). However, the interplay between immunotherapy resistance and NED in NSCLC remains unclear. This study explored the relationships between NED-related genes (NEDRGs) and immunotherapy resistance-related genes in NSCLC.
methodsControl and NSCLC samples, including NSCLC samples exposed to PD-1 blockade, were selected from public databases to identify differentially expressed genes (DEGs). Then, univariate Cox regression analysis and the proportional hazards assumption test were performed to identify prognostic genes based on the DEGs and NEDRGs, and a risk model was developed and validated. Thereafter, a nomogram was established. Subsequently, gene set enrichment analysis (GSEA), immune analysis, and drug sensitivity analysis were conducted. The key cells were ascertained in a single-cell RNA sequencing dataset. We collected specimens from six patients at Tianjin Medical University General Hospital and validated them using quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC).
resultsThree prognostic genes (RRM2, WDR76, and PLEKHH2) were identified, and the developed risk model could predict the survival of patients with NSCLC. The nomogram had good predictive ability concerning survival rates in NSCLC. Based on the GSEA results, a notable pathway in the two risk groups included cell cycle pathways, and prognostic genes were all enriched in these pathways. Furthermore, activated memory CD4
conclusionThe developed risk model based on three prognostic genes (RRM2, WDR76, and PLEKHH2) exhibited superior predictive accuracy in NSCLC. These results may provide new insights for investigating novel therapeutic targets in NSCLC.
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