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:Constructing and validating of m7G-related genes prognostic signature for hepatocellular carcinoma and immune infiltration: potential biomarkers for predicting the overall survival.
Constructing and validating of m7G-related genes prognostic signature for hepatocellular carcinoma and immune infiltration: potential biomarkers for predicting the overall survival.
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LIHC 的发生和进展与 m7G 相关基因有关。相应的预后模型有助于预测 LIHC 患者的预后。TME 中 m7G 相关基因和相关的免疫细胞浸润可能作为 LIHC 的潜在治疗靶点,这需要进一步的试验。此外,m7G 相关基因特征为预测 LIHC 提供了一种可行的替代方法,这些 m7G 相关基因显示了未来 LIHC 靶向治疗的前瞻性研究领域。
探讨N7-甲基鸟苷(m7G)调控因子和免疫浸润在肝细胞癌(LIHC)中的预后意义。
该研究在来自癌症基因组图谱(TCGA)和国际癌症基因组联盟(ICGC)数据集的LIHC样本中测量了预测性m7G基因。基于mRNA表达的干性指数(mRNAsi)、基因突变及相应临床特征的数据均获取自TCGA和ICGC。采用Lasso回归构建预测模型,以评估LIHC中的m7G预后信号。基于这些基因,进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析,以识别关键生物学功能和通路。评估了m7G RNA甲基化调节因子与LIHC预后及免疫浸润之间的相关性。
在LIHC和健康组织中存在21个m7G相关的差异表达基因(DEGs),通过对这些DEGs进行共识聚类,LIHC患者可分为两类。采用最小绝对收缩和选择算子(LASSO)Cox回归分析构建了一个五基因预测模型。低风险组患者的生存率显著高于高风险组(P=0.001)。使用ICGC数据库进行了验证。此外,单因素和多因素Cox回归分析表明,预测模型产生的风险评分是LIHC的独立预测因子[风险比(HR):1.848,95%置信区间(CI):1.286-2.656;HR:2.597,95% CI:1.358-4.965]。ICGC队列的ROC曲线显示,五基因预测模型表现良好[1年曲线下面积(AUC)=0.642,2年AUC=0.686,3年AUC=0.667]。免疫肿瘤学评分显示,在高风险组中,16种免疫细胞中,中性粒细胞和自然杀伤(NK)细胞的表达较低,而调节性T细胞(Tregs)的表达较高。
To investigate the prognostic significance of N7-methylguanosine (m7G) regulators and immune infiltration in liver hepatocellular carcinoma (LIHC).
The research measured predictive m7G genes in LIHC samples from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Data on the stemness index based on mRNA expression (mRNAsi), gene mutations, and corresponding clinical characteristics were obtained from TCGA and ICGC. Lasso regression was used to construct the prediction model to assess the m7G prognostic signals in LIHC. Based on these genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify key biological functions and pathways. The correlation between m7G RNA methylation regulators and the prognosis and immune infiltration of LIHC was evaluated.
There were 21 m7G-related differentially expressed genes (DEGs) in LIHC and healthy tissues, and LIHC patients could be divided into two categories by consensus clustering of these DEGs. A five-gene predictive approach was employed using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Patients in the low-risk group showed a significantly higher survival rate compared with those in the high-risk group (P=0.001). Validations using the ICGC database. Also, univariate and multivariate Cox regression analyses suggested that the risk score produced by the predictive model is an independent predictor for LIHC [hazard ratio (HR): 1.848, 95% confidence interval (CI): 1.286-2.656; HR: 2.597, 95% CI: 1.358-4.965]. The ROC curves of the ICGC cohort revealed that the five-gene prediction model performed well [area under the curve (AUC) =0.642 at 1 year, AUC =0.686 at 2 years, and AUC =0.667 at 3 years]. Immuno-oncology scoring revealed that in the high-risk group, among 16 immune cells, the expressions of neutrophils and natural killer (NK) cells were low and that of regulatory T-cells (Tregs) was high.
LIHC occurrence and progression are linked to m7G-related genes. Corresponding prognostic models help forecast the prognosis of LIHC patients. m7G-related genes and associated immune cell infiltration in the TME may serve as potential therapeutic targets in LIHC, which requires further trials. In addition, the m7G-related gene signature offers a viable alternative to predict LIHC, and these m7G-related genes show a prospective research area for LIHC targeted treatment in the future.
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