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:SNRPD1/E/F/G Serve as Potential Prognostic Biomarkers in Lung Adenocarcinoma.
SNRPD1/E/F/G Serve as Potential Prognostic Biomarkers in Lung Adenocarcinoma.
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参与前体mRNA剪接的Sm蛋白(SNRPB/D1/D2/D3/E/F/G)此前已被报道与多种癌症的肿瘤发生有关。然而,它们在肺腺癌(LUAD)中的具体作用仍不清楚。本研究旨在通过整合生物信息学分析,描述Sm蛋白基因的异常表达和突变,并评估其作为治疗靶点的潜力。
在本研究中,我们通过TCGA、GEO、UALCAN、Oncomine、Metascape、David 6.8和Kaplan-Meier Plotter探讨了Sm蛋白基因在LUAD中的表达模式及预后价值,并通过单因素和多因素cox回归分析证实了其独立预后价值。同时,通过RT-qPCR验证了它们的表达模式。通过cBioPortal数据库分析了Sm蛋白基因的基因突变和共表达。通过STRING和Cytoscape可视化了LUAD中Sm蛋白的PPI网络。使用“GSVA”R包分析了Sm蛋白基因与免疫浸润之间的相关性。
发现Sm蛋白基因在LUAD组织和LUAD细胞系中均表达上调。此外,Sm蛋白的高mRNA表达水平与LUAD的短生存时间密切相关。Sm蛋白基因与Th2细胞浸润呈正相关,但与肥大细胞、Th1细胞和NK细胞浸润呈负相关。重要的是,Cox回归分析显示,高SNRPD1/E/F/G表达是LUAD总生存期的独立危险因素。
我们的研究表明,SNRPD1/E/F/G可独立预测LUAD的预后结局,并与免疫浸润相关。此外,本报告为进一步探索SNRPD1/E/F/G在LUAD中作为潜在治疗靶点的作用奠定了基础。
Objectives: Sm proteins (SNRPB/D1/D2/D3/E/F/G), involved in pre-mRNA splicing, were previously reported in the tumorigenesis of several cancers.
However, their specific role in lung adenocarcinoma (LUAD) remains obscure.
Our study aims to feature abnormal expressions and mutations of genes for Sm proteins and assess their potential as therapeutic targets via integrated bioinformatics analysis. Methods: In this research, we explored the expression pattern and prognostic worth of genes for Sm proteins in LUAD across TCGA, GEO, UALCAN, Oncomine, Metascape, David 6. 8, and Kaplan-Meier Plotter, and confirmed its independent prognostic value via univariate and multivariate cox regression analysis.
Meanwhile, their expression patterns were validated by RT-qPCR. Gene mutations and co-expression of genes for Sm proteins were analyzed by the cBioPortal database. The PPI network for Sm proteins in LUAD was visualized by the STRING and Cytoscape. The correlations between genes for Sm proteins and immune infiltration were analyzed by using the "GSVA" R package. Results: Sm proteins genes were found upregulated expression in both LUAD tissues and LUAD cell lines.
Moreover, highly expressed mRNA levels for Sm proteins were strongly associated with short survival time in LUAD. Genes for Sm proteins were positively connected with the infiltration of Th2 cells, but negatively connected with the infiltration of mast cells, Th1 cells, and NK cells.
Importantly, Cox regression analysis showed that high SNRPD1/E/F/G expression were independent risk factors for the overall survival of LUAD. Conclusion: Our study showed that SNRPD1/E/F/G could independently predict the prognostic outcome of LUAD and was correlated with immune infiltration. Also, this report laid the foundation for additional exploration on the potential treatment target's role of SNRPD1/E/F/G in LUAD.
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