Department of Tumor Center, The Affiliated Jiangyin Hospital of Nantong University, Jiangyin, Jiangsu, 214400, China.
Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China.
Exp Cell Res. 2024 May 1;438(1):114037. doi: 10.1016/j.yexcr.2024.114037. Epub 2024 Apr 16.
Anoikis plays a crucial role in the progression, prognosis, and immune response of lung adenocarcinoma (LUAD). However, its specific impact on LUAD remains unclear. In this study, we investigated the intricate interplay of nesting apoptotic factors in LUAD. By analyzing nine key nesting apoptotic factors, we categorized LUAD patients into two distinct clusters. Further examination of immune cell profiles revealed that Cluster A exhibited greater infiltration of innate immune cells than did Cluster B. Additionally, we identified two genes closely associated with prognosis and developed a predictive model to differentiate patients based on molecular clusters. Our findings suggest that the loss of specific anoikis-related genes could significantly influence the prognosis, tumor microenvironment, and clinical features of LUAD patients. Furthermore, we validated the expression and functional roles of two pivotal prognostic genes, solute carrier family 2 member 1 (SLC2A1) and sphingosine kinase 1 (SPHK1), in regulating tumor cell viability, migration, apoptosis, and anoikis. These results offer valuable insights for future mechanistic investigations. In conclusion, this study provides new avenues for advancing our understanding of LUAD, improving prognostic assessments, and developing more effective immunotherapy strategies.
失巢凋亡在肺腺癌(LUAD)的进展、预后和免疫反应中起着至关重要的作用。然而,其对 LUAD 的具体影响尚不清楚。在本研究中,我们研究了嵌套凋亡因子在 LUAD 中的复杂相互作用。通过分析九个关键的嵌套凋亡因子,我们将 LUAD 患者分为两个不同的簇。进一步检查免疫细胞图谱显示,簇 A 比簇 B 有更多的固有免疫细胞浸润。此外,我们确定了两个与预后密切相关的基因,并开发了一种预测模型,根据分子簇来区分患者。我们的研究结果表明,特定的失巢凋亡相关基因的丢失可能显著影响 LUAD 患者的预后、肿瘤微环境和临床特征。此外,我们验证了两个关键预后基因溶质载体家族 2 成员 1(SLC2A1)和鞘氨醇激酶 1(SPHK1)在调节肿瘤细胞活力、迁移、凋亡和失巢凋亡中的表达和功能作用。这些结果为未来的机制研究提供了有价值的见解。总之,本研究为深入了解 LUAD、改善预后评估和开发更有效的免疫治疗策略提供了新的途径。