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:Correlative Study on the Relationship between the Expression of m6a-Related Genes and the Prognosis and Immunotherapy of Soft Tissue Sarcoma.
Correlative Study on the Relationship between the Expression of m6a-Related Genes and the Prognosis and Immunotherapy of Soft Tissue Sarcoma.
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我们目前的结果表明,m6A 评分可用于评估 STS 患者的生存率,并指导免疫治疗及预测其效果。对 STS 样本不同 m6A 模式的分析有助于理解肿瘤微环境(TME)的多样性和复杂性,并为个性化免疫治疗的临床开发及 STS 患者预后预测提供了新思路。
软组织肉瘤(STS)是起源于间充质组织和交错外胚层神经组织的罕见恶性肿瘤。免疫治疗在STS患者的预后和生存中起着重要作用。然而,目前尚缺乏足够的证据来证实m6A相关基因的预后价值以及评估STS免疫治疗的疗效。
我们使用R软件分析了STS样本中的23个m6A调节因子,并定义了三种STS m6A调节因子的修饰模式。然后,我们构建了m6A评分,并将样本分为高和低两个亚组。最后,我们使用来自GEO数据库的数据验证了结果。
我们发现,m6A 聚类在总生存期(OS)、无进展生存期(PFS)和免疫浸润率方面存在差异。此外,m6A 评分与活化 B 细胞、活化树突状细胞、CD56 bright NK 细胞、辅助 T 细胞和调节性 T 细胞的含量呈正相关。m6A 评分较高的组也表现出较高的 OS 和 PFS 率。在免疫治疗方面,m6A 评分高的 STS 患者表现出更好的结果。一致地,我们在另一个接受抗 PD-1/PD-L1 治疗的患者数据集中也发现了类似的结果。
Soft tissue sarcomas (STS) are rare malignancies arising from mesenchymal tissue and interlacing ectodermal nerve tissue. Immunotherapy plays an important role in the prognosis and survival of STS patients. However, there is insufficient evidence to confirm the prognostic value of m6A-related genes and to evaluate the efficacy of immunotherapy for STS.
We analyzed 23 m6A regulators from STS samples using R software and defined the modification patterns for three STS m6A regulators. Then, we constructed the m6A scores and divided the samples into high and low subgroups. Finally, we used data from the GEO database to verify the results.
We found that the m6A clusters differed in the overall survival (OS), progression-free survival (PFS), and immune infiltration rate. Additionally, the m6A score was positively correlated with the contents of activated B cells, activated dendritic cells, CD56 bright natural killer cells, helper T cells, and regulatory T cells. The group with a higher m6A score also presented higher OS and PFS rates. Regarding immunotherapy, STS patients with a high m6A score presented better results. Consistently, we found similar results in another dataset with patients that received anti-PD-1/PD-L1 therapy.
Our current results indicated that the m6A score can be used to assess the survival rate of STS patients and guide immunotherapy and predict its effects. The analysis of different m6A patterns of STS samples contributed to the understanding of the diversity and complexity of the tumor microenvironment (TME) and provided new ideas for the clinical development of personalized immunotherapy and prediction of the prognosis of STS patients.
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