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:Natural killer cell-related prognosis signature predicts immune response in colon cancer patients.
Natural killer cell-related prognosis signature predicts immune response in colon cancer patients.
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自然杀伤(NK)细胞是先天免疫系统中对抗肿瘤和病毒感染的关键组成部分。结直肠癌(CRC)患者预后较差,免疫治疗工具在CRC治疗中发挥关键作用。
从TCGA和GEO数据库收集CRC患者的公共数据。从广西医科大学附属肿瘤医院收集CRC患者的组织数据。通过最小绝对收缩和选择算子(LASSO)和Cox回归方法开发NK相关预后模型。从不同临床亚组和外部独立验证队列收集验证数据,以验证模型的准确性。此外,收集多个外部独立免疫治疗数据集,以进一步检验NK相关风险评分(NKRS)在预测免疫治疗反应中的价值。通过细胞增殖、凋亡和Western blotting方法检测关键基因的潜在生物学功能。
开发了一种基于NK相关基因的CRC患者新型预后模型,并生成了NKRS。高NKRS组的预后显著较差。基于免疫反应预测,低NKRS患者可能更适合免疫治疗,且对免疫治疗更敏感。敲低SLC2A3后,CRC细胞的增殖率显著降低,凋亡增加。SLC2A3还被发现与TGF-β信号通路相关。
NKRS在预测CRC患者预后状态和免疫治疗反应方面具有潜在应用价值。SLC2A3有潜力作为CRC的治疗靶点。
Background: Natural killer (NK) cells are crucial components of the innate immune system that fight tumors and viral infections. Patients with colorectal cancer (CRC) have a poor prognosis, and immunotherapeutic tools play a key role in the treatment of CRC. Methods: Public data on CRC patients was collected from the TCGA and the GEO databases.
Tissue data of CRC patients were collected from Guangxi Medical University Affiliated Cancer Hospital. An NK-related prognostic model was developed by the least absolute shrinkage and selection operator (LASSO) and Cox regression method. Validation data were collected from different clinical subgroups and an external independent validation cohort to verify the model's accuracy.
In addition, multiple external independent immunotherapy datasets were collected to further examine the value of NK-related risk scores (NKRS) in the prediction of immunotherapy response. Potential biological functions of key genes were examined by methods of cell proliferation, apoptosis and Western blotting. Results: A novel prognostic model for CRC patients based on NK-related genes was developed and NKRS was generated. There was a significantly poorer prognosis among the high-NKRS group.
Based on immune response prediction, patients with low NKRS may be more suitable for immunotherapy and they are more sensitive to immunotherapy. The proliferation rate of CRC cells was significantly reduced and apoptosis of CRC cells was increased after SLC2A3 was knocked down. SLC2A3 was also found to be associated with the TGF-β signaling pathway. Conclusion: NKRS has potential applications for predicting prognostic status and response to immunotherapy in CRC patients. SLC2A3 has potential as a therapeutic target for CRC.
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