RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Diagnosis and Prognosis of Non-small Cell Lung Cancer based on Machine Learning Algorithms.
Diagnosis and Prognosis of Non-small Cell Lung Cancer based on Machine Learning Algorithms.
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我们首次综合运用多种机器学习算法、在线数据库和体外实验,表明 TOP2A 是肺腺癌的潜在生物标志物,并可能促进新治疗策略的开发。
非小细胞肺癌(NSCLC)一直是学术研究的重点。本研究拟通过生物信息学分析识别潜在生物标志物。
从基因表达综合数据库(GEO)下载 3 个数据集,使用 R 软件筛选差异表达基因(DEG)并分析免疫细胞浸润。基因集富集分析(GSEA)显示两组间显著差异功能和通路。进一步采用多种机器学习算法(最小绝对收缩与选择算子 [LASSO] 和支持向量机递归特征消除 [SVM-RFE])筛选诊断标志物;利用多个在线分析平台评估差异基因表达和预后价值,并通过 Western 印迹检测相关基因对体外细胞增殖的影响。
两个数据集共有 181 个 DEG,并筛选出 9 个诊断标志物;这些基因在第三个数据集中也显著过表达。免疫组化和 Western 印迹验证显示,拓扑异构酶 IIα(TOP2A)在肺癌中过表达且与不良预后相关。此外,TOP2A 与 CD8⁺ T 细胞、嗜酸性粒细胞和自然杀伤(NK)细胞等免疫细胞呈负相关。
本研究首次综合采用多种机器学习算法、在线数据库和体外实验,表明 TOP2A 是肺腺癌潜在生物标志物,可能有助于开发新的治疗策略。
Non-small cell lung cancer (NSCLC) has been the subject of intense scholarly debate. We aimed to identify the potential biomarkers via bioinformatics analysis.
Three datasets were downloaded from gene expression omnibus database (GEO). R software was applied to screen differentially expressed genes (DEGs)and analyze immune cell infiltrates. Gene set enrichment analysis (GSEA) showed significant function and pathway in two groups. The diagnostic markers were further investigated by multiple machine learning algorithms (least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE)). Various online analytic platforms were utilized to explore the expression and prognostic value of differential genes. Furthermore, western blotting was performed to test the effects of genes on cell proliferation in vitro.
We identified 181 DEGs shared by two datasets and selected nine diagnostic markers. Those genes were also significantly overexpressed in the third dataset. Topoisomerase II alpha (TOP2A) is overexpressed in lung cancer and associated with a poor prognosis, which was confirmed using immunohistochemistry (IHC) and Western blotting. Additionally, TOP2A showed a negative correlation with immune cells, such as CD8 + T cells, eosinophils and natural killer (NK) cell.
Collectively, for the first time, we applied multiple machine learning algorithms, online databases and experiments in vitro to show that TOP2A is a potential biomarker for lung adenocarcinoma and could facilitate the development of new treatment strategies.
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