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:FYN as an emerging biological biomarker for prognosis and potential therapeutic target in LGG.
FYN as an emerging biological biomarker for prognosis and potential therapeutic target in LGG.
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FYN 在 LGG 中高表达,与其良好预后相关。它参与肿瘤病理生理过程,可能是 LGG 的治疗靶点。
本研究旨在探讨FYN在低级别胶质瘤(LGG)中的表达、临床意义及功能机制。
采用OncoLnc、GEPIA和人类蛋白质图谱(HPA)等数据库检测FYN在LGG组织中的mRNA和蛋白表达。使用UCSC Xena浏览器、TIMER、STRING和Metascape数据库研究Kaplan-Meier生存曲线、FYN表达与各类免疫细胞浸润之间的相关性、蛋白相互作用网络及可能的功能机制。
FYN在LGG、IDH突变或1p19q共缺失亚组中的表达显著高于相应的对照组(p < 0.05)。FYN表达较高的患者总生存期更长(p < 0.05)。男性或1p19q非共缺失组中FYN表达较高者也具有更长的总生存期(p < 0.05)。FYN表达与细胞纯度、CD4+T细胞、巨噬细胞和CD8+T细胞的浸润水平密切相关(p < 0.05)。蛋白互作网络结果显示FYN、SH2D1A、LCK、CAV1、SRC、CBL和PTK2之间存在相关性。功能富集分析揭示FYN及其相关基因主要参与细菌入侵上皮细胞和NK 细胞介导的细胞毒性。肽基-酪氨酸磷酸化、失巢凋亡的负调控、免疫效应过程、跨膜受体蛋白酪氨酸激酶信号通路、表皮生长因子受体信号通路以及蛋白质修饰过程的负调控可能是关键的生物学过程。
This study aimed to explore the expression, clinical significance, and functional mechanism of FYN in lower-grade gliomas (LGG).
The mRNA and protein expression of FYN in LGG tissues were detected using databases including OncoLnc, GEPIA, and Human protein atlas (HPA). The UCSC Xena browser, TIMER, STRING and Metascape databases were used to investigate Kaplan-Meier survival curves, correlations between FYN expression and various types of immune cell infiltration, protein interaction network and possible functional mechanism.
FYN expression in LGG, IDH mutation or 1p19q co-deletion subgroup was significantly higher than in corresponding control groups ( p < 0.05). Patients with higher FYN expression had longer overall survival ( p < 0.05). Male or no 1p19q co-deletion groups with higher FYN expression also had longer overall survival ( p < 0.05). FYN expression had close correlation with infiltrating levels of cell purity, CD4+T cells, macrophages, and CD8+T cells ( p < 0.05). Protein interaction network result showed correlation among FYN, SH2D1A, LCK, CAV1, SRC, CBL and PTK2. Functional enrichment analysis revealed that FYN and its related genes mainly participated in bacterial invasion of epithelial cells and natural killer cell mediated cytotoxicity. Peptidyl-tyrosine phosphorylation, negative regulation of anoikis, immune effector process, transmembrane receptor protein tyrosine kinase signaling pathway, epidermal growth factor receptor signaling pathway, and negative regulation of protein modification process may be the critical biological process.
FYN is up-expressed in LGG and related to its good prognosis. It participated in tumor pathophysiological processes and may be a therapeutic target for LGG.
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