Xu Wanjie, Zhang Jing, Zhang Xinyu, Wang Xue, Xie Yiluo, Min Shengping, Wang Xiaojing, Lian Chaoqun
Department of Clinical Medicine, Bengbu Medical University, Bengbu, China.
Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, The Department of Pulmonary Critical Care Medicine, First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Front Genet. 2025 Jul 8;16:1556366. doi: 10.3389/fgene.2025.1556366. eCollection 2025.
Lipopolysaccharides are involved in malignant progression and epithelial-mesenchymal transition of cancer. The mechanism of LPS in malignant progression of lung adenocarcinoma and possible therapeutic strategies need to be explored.
After obtaining LPS-induced characteristics, 850 samples were characterized. Differences in features were evaluated in different risk subgroups. Cell lines with high scoring performance were selected for experimental validation and possible potential therapeutic options were identified.
By using bioinformatics analysis to obtain LPS signature genes from the LPS induction cohort, the five intersecting genes were utilized to construct a risk model associated with LPS induction. The high-risk score subgroup had a poorer prognosis and lower immunotherapy response, and this subgroup showed distinct EMT features such as hypoxia pathway, high enrichment of WNT pathway and high TP53 mutation. After verifying that the risk model has a close correlation with EMT progression, we obtained cell lines with high EMT-associated features, confirming the possibility of LPS-induced EMT, i.e., demonstrating that LPS acts in inducing EMT progression. The malignant progression of tumors could be inhibited using rosiglitazone and liraglutide combined with lipid-forming trans-differentiation therapy.
In the field of bioinformatics, our study acquired genes characteristic of lipopolysaccharide-induced lung adenocarcinomas and elucidated for the first time that LPS-induced associated scoring patterns correlate with EMT progression. In addition, we propose the possibility of treatment with trans-differentiation therapies that utilize the high plasticity that EMT progressing cancer cells have.
脂多糖参与癌症的恶性进展和上皮-间质转化。脂多糖在肺腺癌恶性进展中的机制及可能的治疗策略有待探索。
在获得脂多糖诱导特征后，对850个样本进行特征分析。在不同风险亚组中评估特征差异。选择评分表现高的细胞系进行实验验证，并确定可能的潜在治疗方案。
通过生物信息学分析从脂多糖诱导队列中获得脂多糖特征基因，利用五个交集基因构建与脂多糖诱导相关的风险模型。高风险评分亚组预后较差且免疫治疗反应较低，该亚组表现出明显的上皮-间质转化特征，如缺氧途径、WNT途径高度富集和TP53高突变。在验证风险模型与上皮-间质转化进展密切相关后，我们获得了具有高上皮-间质转化相关特征的细胞系，证实了脂多糖诱导上皮-间质转化的可能性，即表明脂多糖在诱导上皮-间质转化进展中起作用。使用罗格列酮和利拉鲁肽联合脂质形成转分化疗法可抑制肿瘤的恶性进展。
在生物信息学领域，我们的研究获得了脂多糖诱导的肺腺癌特征基因，并首次阐明脂多糖诱导的相关评分模式与上皮-间质转化进展相关。此外，我们提出利用上皮-间质转化进展癌细胞具有的高可塑性进行转分化疗法治疗的可能性。
