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:A risk score based on polyamine metabolism and chemotherapy-related genes predicts prognosis and immune cells infiltration of lung adenocarcinoma.
A risk score based on polyamine metabolism and chemotherapy-related genes predicts prognosis and immune cells infiltration of lung adenocarcinoma.
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我们旨在探索与铂类治疗和多胺代谢均相关的基因是否能预测LUAD的预后。我们检索了与铂类治疗相关的差异表达基因(DEGs),然后将其与多胺代谢相关基因进行交互,以获得枢纽基因。随后,我们利用scRNA-seq数据分析了LUAD中的主要免疫细胞群体,并评估了不同细胞亚群的多胺代谢活性。筛选高活性组与低活性组之间的DEGs,以识别关键DEGs,从而建立预后风险评分模型。
我们进一步阐明了不同风险组中免疫细胞的景观、突变和药物敏感性分析。最终,我们获得了10个与铂类化疗和多胺代谢均相关的枢纽基因,并发现这些枢纽基因主要影响信号转导通路。基于scRNA-seq数据,B细胞和肥大细胞的多胺代谢活性最高,而NK细胞的多胺代谢活性最低。识别了高多胺代谢活性组与低多胺代谢活性组之间的DEGs,随后筛选出6个关键基因以构建风险评分,其显示出良好的预测能力。该风险评分与免疫治疗检查点基因和细胞毒性T细胞浸润呈普遍负相关。低风险组中EGFR的突变率显著高于高风险组。
总之,我们基于与铂类治疗和多胺代谢相关的关键基因开发了一个风险评分,为LUAD的预后预测提供了新的视角。
We aimed to explore whether the genes associated with both platinum-based therapy and polyamine metabolism could predict the prognosis of LUAD.
We searched for the differential expression genes (DEGs) associated with platinum-based therapy, then we interacted them with polyamine metabolism-related genes to obtain hub genes. Subsequently, we analysed the main immune cell populations in LUAD using the scRNA-seq data, and evaluated the activity of polyamine metabolism of different cell subpopulations. The DEGs between high and low activity groups were screened to identify key DEGs to establish prognostic risk score model.
We further elucidated the landscape of immune cells, mutation and drug sensitivity analysis in different risk groups.
Finally, we got 10 hub genes associated with both platinum-based chemotherapy and polyamine metabolism, and found that these hub genes mainly affected signalling transduction pathways. B cells and mast cells with highest polyamine metabolism activity, while NK cells were found with lowest polyamine metabolism activity based on scRNA-seq data.
DEGs between high and low polyamine metabolism activity groups were identified, then 6 key genes were screened out to build risk score, which showed a good predictive power. The risk score showed a universal negative correlation with immunotherapy checkpoint genes and the cytotoxic T cells infiltration. The mutation rates of EGFR in low-risk group was significantly higher than that of high-risk group.
In conclusion, we developed a risk score based on key genes associated with platinum-based therapy and polyamine metabolism, which provide a new perspective for prognosis prediction of LUAD.
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