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:DNA methylation-regulated SNX20 overexpression correlates with poor prognosis, immune cell infiltration, and low-grade glioma progression.
DNA methylation-regulated SNX20 overexpression correlates with poor prognosis, immune cell infiltration, and low-grade glioma progression.
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我们发现SNX20在LGG中表达上调,其高表达与不良临床结局和较差的临床特征相关,包括WHO分级、IDH突变、1p/19q共缺失和初始治疗结局。Cox回归分析结果显示,SNX20是低级别胶质瘤预后的独立因素。
同时,我们还建立了基于SNX20的列线图,用于预测LGG患者的1年、3年或5年生存率。此外,我们发现DNA低甲基化导致其在LGG中过表达。
另外,功能注释证实SNX20主要参与免疫反应和炎症反应相关信号通路,包括T细胞受体信号通路、NK 细胞介导的细胞毒性和NF-kappa B信号通路。
最后,我们确定SNX20表达增加与LGG中多种免疫细胞浸润水平和免疫检查点相关。重要的是,我们发现SNX20在胶质瘤细胞系中高表达。敲低SNX20显著抑制胶质瘤细胞增殖和迁移能力。这是首个将SNX20鉴定为新的潜在预后生物标志物并表征SNX20在LGG进展中功能作用的研究,并为未来LGG提供了一种新的潜在诊断和治疗生物标志物。
We revealed that SNX20 was up-regulated in LGG, and its higher expression was associated with adverse clinical outcomes and poor clinical characteristics, including WHO grade, IDH mutation, 1p/19q codeletion, and primary therapy outcome. The results of the Cox regression analysis revealed that SNX20 was an independent factor for the prognosis of low-grade glioma. Meanwhile, we also established a nomogram based on SNX20 to predict the 1-, 3-, or 5-year survival in LGG patients.
Furthermore, we found that DNA hypomethylation results in its overexpression in LGG.
In addition, functional annotation confirmed that SNX20 was mainly involved in the immune response and inflammatory response related signaling pathways, including the T cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, and the NF-kappa B signaling pathway.
Finally, we determined that increased expression of SNX20 was correlated with infiltration levels of various immune cells and immune checkpoint in LGG.
Importantly, we found that SNX20 was highly expressed in glioma cell lines. Depletion of SNX20 significantly inhibits glioma cell proliferation and migration abilities. This is the first study to identify SNX20 as a new potential prognostic biomarker and characterize the functional roles of SNX20 in the progression of LGG, and provides a novel potential diagnostic and therapeutic biomarker for LGG in the future.
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