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:PLOD3 as a novel oncogene in prognostic and immune infiltration risk model based on multi-machine learning in cervical cancer.
PLOD3 as a novel oncogene in prognostic and immune infiltration risk model based on multi-machine learning in cervical cancer.
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宫颈癌(CC)尽管在筛查和治疗方面取得了进展,仍是全球重要的健康问题。为提高预后准确性和治疗策略,我们开发了一种基于代谢相关基因的多机器学习预后模型。
本研究整合了来自多个数据库的基因组、转录组和空间数据,以识别与CC具有因果关系的关键代谢基因。我们识别出112个关键代谢基因,并通过多种机器学习算法构建并验证了预后模型。GO和KEGG富集分析显示MAPK级联在代谢过程中发挥关键作用。为确定关键代谢基因,我们构建了WGCNA并提取了337个关键基因。监督主成分分析和随机生存森林被纳入最终模型,该模型在患者分类方面显示出强大的预测能力。
此外,该模型在不同风险类别间显示出免疫细胞浸润的显著差异,表明调节性T细胞可能参与免疫抑制,而NK 细胞在肿瘤清除中的作用可能有限。空间转录组学和单细胞分析进一步验证了该模型,揭示了与不同风险水平相关的肿瘤异质性和不同的细胞间通讯模式。功能实验结果表明,PLOD3的下调可抑制CC细胞的增殖。
在本研究中,我们提供了一种预测患者结局的精准医学方法,以及对代谢基础的新见解,这可能有助于CC的预后和免疫治疗。此外,我们发现PLOD3是CC中的一种新型癌基因。这些发现表明,该模型可用于评估CC患者的预后风险并识别潜在的治疗靶点。
Cervical carcinoma (CC) remains a significant global health issue despite advancements in screening and treatment. To improve prognostic accuracy and therapeutic strategies, we developed a multi-machine learning prognostic model based on metabolic-associated genes.
This study integrated genomic, transcriptomic, and spatial data from multiple databases to identify key metabolic genes with a causal relationship to CC.
We identified 112 key metabolic genes, which were used to construct and validate a prognostic model through various machine learning algorithms. GO and KEGG enrichment analysis revealed the MAPK cascade plays a crucial role in metabolic processes. To pinpoint key metabolic genes, we constructed WGCNA and extracted 337 key genes. Supervised principal component analysis and random survival forests were incorporated into the final model, which showed strong predictive ability in classifying patients.
Furthermore, the model demonstrated notable variations in immune cell infiltration among risk categories, which shown regulatory T cells may be involved in immune suppression, and natural killer cells might have a limited effect in tumor clearance. Spatial transcriptomics and single-cell analyses further validated the model, uncovering tumor heterogeneity and distinct intercellular communication patterns associated with different risk levels.
The functional experiment results indicated that down expression of PLOD3 could suppress the proliferation of CC cell. In this study, offer a precision medicine methods for predicting patient outcomes as well as fresh insights into the metabolic foundations, which may contribute to the prognosis and immunotherapy of CC.
Additionally, we discovered PLOD3 to be a novel oncogene in CC.
These findings imply that this model may be applied to assess prognostic risk and identify potential therapeutic targets for CC patients.
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