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:Construction and validation of risk models of prognostic genes associated with parthanatos in papillary thyroid carcinoma based on bioinformatics.
Construction and validation of risk models of prognostic genes associated with parthanatos in papillary thyroid carcinoma based on bioinformatics.
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本研究全面绘制了 PTC 中的 PRGs 图谱,建立了经过验证的风险模型,并为免疫微环境相互作用及治疗靶点提供了见解,推动了 PTC 的精准肿瘤学发展。
利用GSE33630数据集,鉴定差异表达的PRGs,并通过加权基因共表达网络分析(WGCNA)进行分析,以确定关键模块基因。回归分析筛选出7个预后基因用于风险模型构建。验证了模型的性能,并开发了列线图用于生存预测。进一步分析包括临床特征相关性、免疫浸润、药物敏感性、基因集富集分析(GSEA),以及通过RT-qPCR进行实验验证。
鉴定出7个预后基因(TSHZ3、SERGEF、AKAP12、SGPP2、ASGR1、AK1、PELI2)。该风险模型展现出稳健的预测准确性,可将患者分为高风险组和低风险组,两组间生存差异显著。GSEA揭示了29条富集通路(如核糖体、黏着斑),而免疫浸润分析突出显示CD56 + NK细胞和AK1为关键免疫相关因子。药物敏感性筛选鉴定出111种差异性治疗药物。功能分析表明,AKAP12在预后基因中具有最强的功能相似性。
Using the GSE33630 dataset, differentially expressed PRGs were identified and analyzed via weighted gene co-expression network analysis (WGCNA) to pinpoint key module genes. Regression analysis selected seven prognostic genes for risk model construction. The model's performance was validated, and a nomogram was developed for survival prediction. Further analyses included clinical feature correlations, immune infiltration, drug sensitivity, gene set enrichment analysis (GSEA), and experimental validation via RT-qPCR.
Seven prognostic genes (TSHZ3, SERGEF, AKAP12, SGPP2, ASGR1, AK1, PELI2) were identified. The risk model demonstrated robust predictive accuracy, stratifying patients into high- and low-risk groups with significant survival differences. GSEA revealed 29 enriched pathways (e.g., ribosome, focal adhesion), while immune infiltration analysis highlighted CD56 + NK cells and AK1 as key immune correlates. Drug sensitivity screening identified 111 differential therapeutics. Functional analysis indicated AKAP12 had the strongest functional similarity among prognostic genes.
This study comprehensively mapped PRGs in PTC, established a validated risk model, and provided insights into immune-microenvironment interactions and therapeutic targets, advancing precision oncology for PTC.
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