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
一项与胶质瘤生存和免疫微环境相关的焦亡相关基因预后指数
英文原题：A Pyroptosis-Related Gene Prognostic Index Correlated with Survival and Immune Microenvironment in Glioma.
查看英文原题
A Pyroptosis-Related Gene Prognostic Index Correlated with Survival and Immune Microenvironment in Glioma.
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研究概要
构建的 PRGPI 可用于预测胶质瘤患者的预后并指导个体化免疫治疗。
研究思路结论见上方概要
目的
作为一种炎症形式的程序性细胞死亡，细胞焦亡已被充分证实与肿瘤发生和肿瘤免疫微环境相关。本文旨在构建细胞焦亡相关基因预后指数（PRGPI），用于预测胶质瘤患者的预后并指导个体化免疫治疗。
方法
基于对已发表文献的详细回顾，识别了焦亡相关基因（PRGs）。胶质瘤患者的转录组数据和临床信息来自CGGA和TCGA数据库。采用多因素Cox回归方法构建了PRGPI。通过CIBERSORT算法分析免疫细胞浸润水平。应用肿瘤免疫功能障碍和排斥（TIDE）算法评估对免疫检查点抑制剂（ICI）治疗的潜在反应。在细胞系和病理标本中验证了PRGPI中PRGs的表达模式。
结果
我们共鉴定出31个PRGs。其中，选取PRGs（CASP3、DPP9、MAPK8、PELP1和TOMM20）用于构建PRGPI。在训练队列（CGGA693）和验证队列（CGGA325和TCGA）中，PRGPI-high患者相比PRGPI-low患者表现出更差的生存结局。ROC曲线表明PRGPI的预后预测能力稳健。基于独立预后指标（PRGPI、年龄和WHO分级）开发了列线图，并且对总生存期（OS）也表现出较强的预测能力。此外，PRGPI-high患者表现出更高的免疫、基质和ESTIMATE评分，更低的肿瘤纯度，更高的M2型巨噬细胞浸润，更低的CD8 + T细胞和活化NK细胞浸润，更高的肿瘤突变负荷（TMB），以及更高的免疫检查点表达。TIDE显示，PRGPI-high组中ICI治疗应答者多于PRGPI-low组。最后，PRGPI中5个所选PRGs在正常组织和胶质瘤之间的表达模式存在显著差异。
展开英文摘要原文
PURPOSE
As an inflammatory form of programmed cell death, pyroptosis has been well established to be associated with tumorigenesis and tumor immune microenvironment. In this paper, we aimed at the construction of a pyroptosis-related gene prognostic index (PRGPI) for predicting prognosis and guiding individualized immunotherapy in glioma patients.
PATIENTS AND METHODS
Pyroptosis-related genes (PRGs) were identified based on a detailed review of published literatures. The transcriptome data and clinical information of glioma patients were obtained from CGGA and TCGA databases. PRGPI was constructed by using the multivariate Cox regression method. The immune cell infiltration level was analyzed via CIBERSORT algorithm. The tumor immune dysfunction and exclusion (TIDE) algorithm was applied to evaluate the potential response to immune checkpoint inhibitor (ICI) therapy. The expression patterns of PRGs in PRGPI were validated in cell lines and pathological specimens.
RESULTS
We identified a total of 31 PRGs. Among them, PRGs (CASP3, DPP9, MAPK8, PELP1 and TOMM20) were selected for the construction of PRGPI. In both training (CGGA693) and validation (CGGA325 and TCGA) cohorts, PRGPI-high patients showed an inferior survival outcome compared with PRGPI-low patients. ROC curves illustrated that the prognostic prediction power of PRGPI was robust. A nomogram was developed based on independent prognostic indicators (PRGPI, age and WHO grade), and also exhibited a strong forecasting ability for overall survival (OS). Additionally, PRGPI-high patients exhibited higher immune, stroma and ESTIMATE scores, lower tumor purity, higher infiltration of M2-type macrophages, lower infiltration of CD8 + T cells and activated NK cells, higher tumor mutation burden (TMB), and higher expression of immune checkpoints. TIDE showed that PRGPI-high group had more responders of ICI therapy than PRGPI-low group. Finally, the expression patterns of five selected PRGs in PRGPI were significantly different between normal and glioma.
CONCLUSION
The constructed PRGPI can be used for predicting prognosis and guiding individualized immunotherapy in glioma patients.
论文信息
- 作者
- Zheng J、Zhou Z、Qiu Y、Wang M、Yu H、Wu Z、Wang X、Jiang X
- 单位
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.China
- 期刊
- Journal of inflammation research2022
- 原文标识
- PubMed 35018108 · DOI 10.2147/JIR.S341774
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