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机器学习模型揭示了ARHGAP11A对非小细胞肺癌淋巴结转移和干性的影响。

Machine learning models reveal ARHGAP11A's impact on lymph node metastasis and stemness in NSCLC.

作者信息

Wang Xiaoli, Zhou Yan, Lu Xiaomin, Shao Lili

机构信息

Department of Oncology, Tumor Hospital Affiliated to Nantong University, Nantong, China.

Department of Oncology, Affiliated Haian Hospital of Nantong University, Nantong, China.

出版信息

Biofactors. 2025 Jan-Feb;51(1):e2141. doi: 10.1002/biof.2141. Epub 2024 Oct 31.

Abstract

Most patients with non-small cell lung cancer (NSCLC) are diagnosed at an advanced stage of the disease, which complicates treatment due to a heightened risk of metastasis. Consequently, the timely identification of biomarkers associated with lymph node metastasis is essential for improving the clinical management of NSCLC patients. In this research, the WGCNA algorithm was utilized to pinpoint genes linked to lymph node metastasis in NSCLC. A cluster analysis was carried out to investigate how these genes correlate with the prognosis and the outcomes of immunotherapy for NSCLC patients. Following this, diagnostic and prognostic models were created and validated through various machine learning methodologies. The random forest technique highlighted the importance of ARHGAP11A, leading to an in-depth examination of its role in NSCLC. By analyzing 78 tissue chip samples from NSCLC patients, the study confirmed the association between ARHGAP11A expression, patient prognosis, and lymph node metastasis. Finally, the influence of ARHGAP11A on NSCLC cells was assessed through cell function experiments. This research utilized the WGCNA technique to identify 25 genes that are related to lymph node metastasis, clarifying their connections with tumor invasion, growth, and the activation of stemness pathways. Cluster analysis revealed significant associations between these genes and lymph node metastasis in NSCLC, especially concerning immunotherapy and targeted treatments. A diagnostic system that combines various machine learning approaches demonstrated strong efficacy in forecasting both the diagnosis and prognosis of NSCLC. Importantly, ARHGAP11A was identified as a key prognostic gene associated with lymph node metastasis in NSCLC. Molecular docking analyses suggested that ARHGAP11A has a strong affinity for targeted therapies within NSCLC. Additionally, immunohistochemical assessments confirmed that higher levels of ARHGAP11A expression correlate with unfavorable outcomes for NSCLC patients. Experiments on cells showed that reducing ARHGAP11A expression can hinder the proliferation, metastasis, and stemness traits of NSCLC cells. This investigation reveals the novel insight that ARHGAP11A may function as a potential biomarker connected to lymph node metastasis in NSCLC. Moreover, reducing the expression of ARHGAP11A has demonstrated the ability to diminish tumor stemness characteristics, presenting a promising opportunity for improving treatment strategies for this condition.

摘要

大多数非小细胞肺癌(NSCLC)患者在疾病晚期被诊断出来,由于转移风险增加,这使得治疗变得复杂。因此,及时识别与淋巴结转移相关的生物标志物对于改善NSCLC患者的临床管理至关重要。在本研究中,利用加权基因共表达网络分析(WGCNA)算法来确定与NSCLC淋巴结转移相关的基因。进行聚类分析以研究这些基因如何与NSCLC患者的预后和免疫治疗结果相关联。随后,通过各种机器学习方法创建并验证了诊断和预后模型。随机森林技术突出了ARHGAP11A的重要性,从而对其在NSCLC中的作用进行了深入研究。通过分析78例NSCLC患者的组织芯片样本,该研究证实了ARHGAP11A表达、患者预后和淋巴结转移之间的关联。最后,通过细胞功能实验评估了ARHGAP11A对NSCLC细胞的影响。本研究利用WGCNA技术鉴定了25个与淋巴结转移相关的基因,阐明了它们与肿瘤侵袭、生长和干性途径激活的联系。聚类分析揭示了这些基因与NSCLC淋巴结转移之间的显著关联,特别是在免疫治疗和靶向治疗方面。结合各种机器学习方法的诊断系统在预测NSCLC的诊断和预后方面显示出强大的功效。重要的是,ARHGAP11A被确定为与NSCLC淋巴结转移相关的关键预后基因。分子对接分析表明,ARHGAP11A对NSCLC中的靶向治疗具有很强的亲和力。此外,免疫组织化学评估证实,ARHGAP11A表达水平较高与NSCLC患者预后不良相关。细胞实验表明,降低ARHGAP11A表达可阻碍NSCLC细胞的增殖、转移和干性特征。这项研究揭示了新的见解,即ARHGAP11A可能作为与NSCLC淋巴结转移相关的潜在生物标志物发挥作用。此外,降低ARHGAP11A的表达已证明能够减少肿瘤干性特征,为改善这种疾病的治疗策略提供了一个有前景的机会。

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