Cellular senescence is involved in critical processes in tumor progression. Despite this potential relationship, the relationship between tumor cell senescence, prognostic significance, spread through air spaces (STAS), and tumor histology has not been investigated in lung adenocarcinoma (LUAD). We used the LUAD PanCancer Atlas dataset to assess senescence cell signature (SCS) based on the SenMayo gene set. We examined the relationship between SCS, prognostic significance, STAS, and tumor histology. This relationship was confirmed in independent LUAD datasets by validation using immunohistochemical senescence markers. In the LUAD PanCancer Atlas dataset, patients with high SCS expression had a higher prevalence of solid histology and STAS patterns than those with low SCS expression. In the independent LUAD datasets, high p21 expression and low HMGB1 expression were correlated with solid histology or STAS patterns. SCS level was also independent prognostic factor in four different LUAD datasets. The HMGB1 expression was an independent prognostic factor in the independent LUAD dataset in multivariate analysis. The expression of p21 and the presence of solid histology were linked to the epithelial–mesenchymal transition (EMT) phenotype. In LUAD cell lines, inducing senescence with a DNA-damaging agent led to an increase in EMT marker expression. Our findings suggest a strong link between senescence, EMT, and solid histology, offering valuable insight into how cancer cell senescence may promote tumor progression through particular pathways.

细胞衰老参与肿瘤进展的关键过程。尽管存在这种潜在关系，但尚未在肺腺癌 （LUAD） 中研究肿瘤细胞衰老、预后意义、通过空气空间传播 （STAS） 和肿瘤组织学之间的关系。我们使用 LUAD PanCancer Atlas 数据集来评估基于 SenMayo 基因集的衰老细胞特征 （SCS）。我们检查了 SCS 、预后意义、STAS 和肿瘤组织学之间的关系。通过使用免疫组织化学衰老标记物进行验证，在独立的 LUAD 数据集中证实了这种关系。在 LUAD PanCancer Atlas 数据集中，SCS 高表达的患者比 SCS 表达低的患者具有更高的实性组织学和 STAS 模式患病率。在独立的 LUAD 数据集中，高 p21 表达和低 HMGB1 表达与实体组织学或 STAS 模式相关。SCS 水平也是 4 个不同 LUAD 数据集的独立预后因素。在多变量分析中，HMGB1 表达是独立 LUAD 数据集中的独立预后因素。p21 的表达和实体组织学的存在与上皮-间充质转化 （EMT） 表型有关。在 LUAD 细胞系中，用 DNA 损伤剂诱导衰老导致 EMT 标志物表达增加。我们的研究结果表明衰老、EMT 和实体组织学之间存在密切联系，为癌细胞衰老如何通过特定途径促进肿瘤进展提供了有价值的见解。