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:DcR3-associated risk score: correlating better prognosis and enhanced predictive power in colorectal cancer.
DcR3-associated risk score: correlating better prognosis and enhanced predictive power in colorectal cancer.
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诱骗受体 3(DcR3)是一种属于肿瘤坏死因子受体(TNFR)家族的新型可溶性蛋白,既往研究发现其与多种癌症的肿瘤发生相关。
然而,本研究意外发现 DcR3 可能延长结直肠癌(CRC)患者生存时间。通过分析癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)数据集,我们发现 DcR3 高表达与 CRC 患者总生存期(OS)和无病生存期(DFS)改善相关。
进一步分析显示,DcR3 与无远处转移(M0)及 I/II 期 CRC 患者的良好临床特征相关,提示其可能在 CRC 中发挥抑制作用。基因集富集分析(GSEA)显示,DcR3 高表达组富集 IL-17 信号通路及其他免疫相关通路;单样本基因集富集分析(ssGSEA)则发现,DcR3 高表达组TIL(肿瘤浸润淋巴细胞)丰度较高。为深入理解 DcR3 功能,我们使用机器学习构建 DcR3 相关风险评分(DARS)模型,包含 3 个基因:DPP7、KDM3A 和 TMEM86B。DARS 模型显示,风险评分高的患者预后较差,且与晚期(III/IV 期)、T3/4 肿瘤及 N1/2 淋巴结受累相关。
此外,高风险组 TTN、MUC16 和 SYNE1 等基因突变更常见,其中 SYNE1 突变与预后不良有关。有趣的是,低风险组 DcR3 表达较高。这些结果提示 DcR3 可能成为 CRC 的预后生物标志物,并可能在良性调节该恶性肿瘤免疫反应中发挥关键作用。
Decoy receptor 3 (DcR3), a novel soluble protein belonging to the tumor necrosis factor receptor (TNFR) family, has been previously associated with tumorigenesis in various cancers.
However, in our study, we unexpectedly found that DcR3 may promote patient survival time in colorectal cancer (CRC). Through an analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we discovered that high levels of DcR3 are associated with improved overall survival (OS) and disease-free survival (DFS) in CRC patients.
Further investigation revealed that DcR3 is correlated with favorable clinical features in Metastasis 0 (M0) and stage I/II CRC patients, suggesting it may act as a suppressive factor in CRC. Gene Set Enrichment Analysis (GSEA) demonstrated that the high DcR3 group is enriched in the IL-17 signaling pathway and other immune-related pathways, and Single Sample Gene Set Enrichment Analysis (ssGSEA) revealed a higher abundance of Tumor Infiltrating Lymphocytes (TIL) in the DcR3 high group.
To better understand the function of DcR3, we constructed a DcR3-associated riskscore (DARS) model using machine learning, comprising three genes (DPP7, KDM3A, and TMEM86B). The DARS model indicated that high riskscore patients have an unfavorable prognosis, and it is associated with advanced stages (III/IV), T3/4 tumors, and N1/2 lymph node involvement.
Additionally, high riskscore group exhibited more frequent gene mutations, such as TTN, MUC16, and SYNE1, with SYNE1 mutation being related to poor prognosis. Intriguingly, DcR3 showed higher expression in the low riskscore group. These results suggest that DcR3 could serve as a potential prognostic biomarker in CRC and may play a crucial role in favorably modulating the immune response in this malignancy.
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