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:Machine Learning-Based Glycolipid Metabolism Gene Signature Predicts Prognosis and Immune Landscape in Oesophageal Squamous Cell Carcinoma.
Machine Learning-Based Glycolipid Metabolism Gene Signature Predicts Prognosis and Immune Landscape in Oesophageal Squamous Cell Carcinoma.
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我们采用机器学习方法,基于糖脂代谢相关基因开发并验证了一种新的食管鳞状细胞癌(ESCC)预后模型。通过对TCGA和GEO数据集的整合分析,我们建立了一个稳健的15基因特征,能够有效将患者分为不同的风险组。该特征表现出优越的预后价值,并揭示了与免疫浸润模式的显著关联。高风险患者表现出免疫细胞浸润减少,尤其是B细胞和NK细胞,同时肿瘤纯度增加。单细胞RNA测序分析揭示了高风险组中独特的细胞组成模式和增强的相互作用强度,尤其是在上皮细胞和平滑肌细胞中。功能验证证实MECP2是一个有前景的治疗靶点,其敲低在体外和体内均显著抑制肿瘤进展。药物敏感性分析确定了特定治疗药物对高风险患者显示出潜在疗效。我们的研究既提供了一种实用的预后工具,也为ESCC中糖脂代谢与肿瘤免疫之间的关系提供了新的见解,为个性化治疗提供了潜在策略。
Using machine learning approaches, we developed and validated a novel prognostic model for oesophageal squamous cell carcinoma (ESCC) based on glycolipid metabolism-related genes. Through integrated analysis of TCGA and GEO datasets, we established a robust 15-gene signature that effectively stratified patients into distinct risk groups. This signature demonstrated superior prognostic value and revealed significant associations with immune infiltration patterns. High-risk patients exhibited reduced immune cell infiltration, particularly in B cells and NK cells, alongside increased tumour purity.
Single-cell RNA sequencing analysis uncovered unique cellular composition patterns and enhanced interaction intensities in the high-risk group, especially within epithelial and smooth muscle cells. Functional validation confirmed MECP2 as a promising therapeutic target, with its knockdown significantly inhibiting tumour progression both in vitro and in vivo. Drug sensitivity analysis identified specific therapeutic agents showing potential efficacy for high-risk patients.
Our study provides both a practical prognostic tool and novel insights into the relationship between glycolipid metabolism and tumour immunity in ESCC, offering potential strategies for personalised treatment.
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