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
将循环肿瘤细胞的 DNA 甲基化标志物与免疫浸润细胞相结合，以评估 III-IV 期结直肠癌的复发和预后，并提出治疗策略
英文原题：Combining the DNA methylation markers of circulating tumor cells with immune infiltrating cells to assess recurrence and prognosis and to suggest a therapeutic strategy in stage III-IV colorectal cancer.
查看英文原题
Combining the DNA methylation markers of circulating tumor cells with immune infiltrating cells to assess recurrence and prognosis and to suggest a therapeutic strategy in stage III-IV colorectal cancer.
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研究概要
ZNF671 和 ZNF132 甲基化水平与 Immunoscore 呈负相关，可能作为 CRC 免疫治疗的有价值生物标志物。这些发现为改进预后评估和个性化治疗策略提供了见解。
研究思路结论见上方概要
背景
循环肿瘤DNA（ctDNA）甲基化标志物在癌症转移的早期检测中显示出潜力。本研究旨在识别可预测结直肠癌（CRC）患者复发和预后的ctDNA甲基化标志物，并探讨肿瘤免疫微环境对结局的影响。
方法
我们分析了来自血浆和组织样本的603个重叠甲基化标志物，并开发了一个风险模型来预测CRC复发和预后。
结果
ZNF671和ZNF132被确定为关键甲基化标志物。该模型预测III期CRC患者复发风险的AUC为0.90，并预测IV期患者的预后。高风险患者的早期复发率显著更高（75.4% vs. 20%），且更可能具有低Immunoscore（IS），这与较差的预后相关。
展开英文摘要原文
METHODS
We analyzed 603 overlapping methylation markers from both plasma and tissue samples and developed a risk model to predict CRC recurrence and prognosis.
RESULTS
ZNF671 and ZNF132 were identified as key methylation markers. The model predicted relapse risk in stage III CRC patients with an AUC of 0.90 and prognosis in stage IV patients. High-risk patients exhibited a significantly higher early relapse rate (75.4% vs. 20%) and were more likely to have a low Immunoscore (IS), which correlates with poorer prognosis. DISCUSSION: ZNF671 and ZNF132 methylation levels inversely correlate with Immunoscore and may serve as valuable biomarkers for CRC immunotherapy. These findings provide insights for improved prognostic evaluation and personalized treatment strategies.
论文信息
- 作者
- Zhou J、Ye D、Li Y、Lai X、Cui W、He W、Yu L、Wu J
- 第一作者单位
- Department of Oncology, General Hospital of Southern Theater Command, People's Liberation Army of China, Guangzhou, China.China
- 通讯作者单位
- Department of Pathology, General Hospital of Southern Theater Command, People's Liberation Army of China, Guangzhou, China.China
- 期刊
- Frontiers in immunology2025
- 原文标识
- PubMed 40791581 · DOI 10.3389/fimmu.2025.1607548
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