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:Comprehensive analysis indicates DDX46 as a novel biomarker for the prognosis of lung adenocarcinoma.
Comprehensive analysis indicates DDX46 as a novel biomarker for the prognosis of lung adenocarcinoma.
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DEAD-box 46(DDX46)在多种恶性肿瘤中表达水平升高;然而,DDX46 在肺腺癌(LUAD)中的功能,包括其表达模式及功能意义,尚未完全阐明。
本研究主要探讨 DDX46 在 LUAD 恶性进展中的潜在作用及潜在机制。本研究分析了公开数据库和临床标本,以评估 DDX46 在 LUAD 中的表达并探讨其预后意义。研究结果表明,与 DDX46 低表达相比,DDX46 高表达与 LUAD 患者更差的预后相关。功能实验,包括 CCK-8、集落形成、5-ethynyl-2'-deoxyuridine 掺入、流式细胞术、伤口愈合和 Transwell 实验,表明沉默 DDX46 可抑制癌细胞迁移、增强凋亡并诱导 G 0 /G 1 期细胞周期阻滞。
此外,DDX46 表达与 T 细胞、NK 细胞和单核细胞的浸润相关,也与多个免疫检查点和趋化因子相关。另外,结果还发现 DDX46 与 LUAD 中的 Wnt 信号通路存在显著关联。DDX46 低表达也被证明与患者药物反应性增加相关。
总之,DDX46 有望成为 LUAD 患者诊断和治疗的双用途标志物。
The expression levels of DEAD-box 46 (DDX46) are elevated in several malignancies; however, the function of DDX46 in lung adenocarcinoma (LUAD), including its expression patterns and functional implications, has not been fully elucidated. The present study primarily explores the potential role and underlying mechanism of DDX46 in the malignant progression of LUAD. The present study analyzed both publicly available databases and clinical specimens to assess DDX46 expression in LUAD and explore its prognostic significance.
The findings demonstrated that elevated DDX46 expression was associated with a worse prognosis in patients with LUAD in comparison with a low DDX46 expression. Functional assays, including Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine incorporation, flow cytometry, wound healing and Transwell assays, indicated that silencing DDX46 suppressed cancer cell migration, enhanced apoptosis, and induced G 0 /G 1 phase cell cycle arrest.
Moreover, DDX46 expression was correlated with the infiltration of T cells, natural killer cells and monocytes, as well as with several immune checkpoints and chemokines.
Additionally, the results identified a marked association between DDX46 and the Wnt signaling pathway in LUAD. Low DDX46 expression was also demonstrated to be associated with increased drug responsiveness in patients.
In conclusion, DDX46 holds promise as a dual-purpose marker for the diagnosis and therapy of patients with LUAD.
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