肺腺癌与肺鳞癌N1淋巴结转移对预后影响的差异及相关机制初探OA

Objective To investigate the differences in prognostic impact of N1 lymph node metastasis between patients with lung adenocarcinoma(LUAD)and lung squamous cell carcinoma(LUSC),as well as the potential mechanisms.Methods A retrospective analysis was performed on 3 441 patients who underwent radical resection for lung cancer between January 2007 and May 2025,including 2 977 cases of invasive LUAD and 464 cases of LUSC.Kaplan-Meier survival curves were used to analyze the effect of N1 metastasis on overall survival(OS),and the results were validated using The Cancer Genome Atlas(TCGA)database.Differential expression genes(DEGs)associated with N1 metastasis in LUAD and LUSC were screened by DESeq2,followed by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The tumor immune microenvironment was analyzed using the Estimate and Cibersort packages.Results OS was significantly shorter in LUAD patients with N1 metastasis than those without N1 metastasis(P＜0.001),whereas no significant difference was observed in OS between LUSC patients with and without N1 metastasis(P=0.387).A total of 1 992 N1-related DEGs were identified between LUAD and LUSC from the TCGA database.Enrichment analysis showed that upregulated genes in N1-positive LUAD were associated with signaling pathways related to cell migration,motility and extracellular matrix-receptor interactions,whereas upregulated genes in N1-positive LUSC were mainly enriched in mitochondrial function and energy metabolism pathways.Immune microenvironment analysis revealed that N1-positive LUAD was enriched in immunosuppressive cells such as resting CD4+memory T cells,M2 macrophages and resting dendritic cells,while N1-positive LUSC was predominantly infiltrated with immunocompetent cells including activated CD4+memory T cells and M0/M1 macrophages.Conclusion The OS of patients with LUAD accompanied by N1 metastasis was significantly shorter than that of patients without metastasis,while LUSC accompanied by N1 metastasis had no significant effect on the OS of patients.Upregulated genes in N1-positive LUAD are involved in cell migration and extracellular matrix-related pathways,with immunosuppressive cells dominated in tumor microenvironment.In contrast,upregulated genes in N1-positive LUSC are enriched in energy metabolism pathways with fewer immunosuppressive cells.Clinically,more aggressive comprehensive therapy should be adopted for LUAD patients with N1 metastasis to control the risk of micrometastasis and improve prognosis.