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:Establishment and validation of an immune infiltration predictive model for ovarian cancer.
Establishment and validation of an immune infiltration predictive model for ovarian cancer.
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IPM 模型可能识别高风险患者,并整合其他临床参数以预测其总生存期,提示其是一种优化卵巢癌预后的潜在方法。
卵巢癌中最常见的突变是 TP53 突变,它影响着疾病的发展和预后。我们研究了 TP53 突变如何与卵巢癌的免疫表型及疾病预后相关联。
我们研究了不同文化群体和数据集中的TP53突变状态和表达谱,并开发了一种免疫浸润预测模型,该模型依赖于TP53 WT和TP53 MUT卵巢癌病例之间差异表达的免疫相关基因。我们旨在构建一种免疫浸润预测模型(IPM),以提高卵巢癌的预后并研究IPM对免疫微环境的影响。
TP53突变影响了77个免疫应答相关基因的表达。实施并评估了一种IPM,用于区分卵巢癌患者中低IPM和高IPM亚组的生存不良个体。因此,创建了一个列线图用于诊断和治疗用途。根据通路富集分析,人类免疫应答和免疫功能异常通路是与IPM基因最相关的功能和通路。此外,高风险组患者显示巨噬细胞M1、活化NK细胞、CD8+ T细胞比例较低,且CTLA-4、PD-1、PD-L1和TIM-3高于低风险组患者。
The most prevalent mutation in ovarian cancer is the TP53 mutation, which impacts the development and prognosis of the disease. We looked at how the TP53 mutation associates the immunophenotype of ovarian cancer and the prognosis of the disease.
We investigated the state of TP53 mutations and expression profiles in culturally diverse groups and datasets and developed an immune infiltration predictive model relying on immune-associated genes differently expressed between TP53 WT and TP53 MUT ovarian cancer cases. We aimed to construct an immune infiltration predictive model (IPM) to enhance the prognosis of ovarian cancer and investigate the impact of the IPM on the immunological microenvironment.
TP53 mutagenesis affected the expression of seventy-seven immune response-associated genes. An IPM was implemented and evaluated on ovarian cancer patients to distinguish individuals with low- and high-IPM subgroups of poor survival. For diagnostic and therapeutic use, a nomogram is thus created. According to pathway enrichment analysis, the pathways of the human immune response and immune function abnormalities were the most associated functions and pathways with the IPM genes. Furthermore, patients in the high-risk group showed low proportions of macrophages M1, activated NK cells, CD8 + T cells, and higher CTLA-4, PD-1, PD-L1, and TIM-3 than patients in the low-risk group.
The IPM model may identify high-risk patients and integrate other clinical parameters to predict their overall survival, suggesting it is a potential methodology for optimizing ovarian cancer prognosis.
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