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:Prognostic prediction of systemic immune-inflammation status for patients with colorectal cancer: a novel pyroptosis-related model.
Prognostic prediction of systemic immune-inflammation status for patients with colorectal cancer: a novel pyroptosis-related model.
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细胞焦亡及相关gasdermin家族蛋白在结直肠癌(CRC)的肿瘤发生中发挥重要作用。然而,细胞焦亡相关基因(PRGs)的预后作用及其与CRC发病机制中免疫细胞浸润的关系仍不清楚。
在本研究中,我们基于13个PRGs(AIM2、CASP1、CASP5、CASP6、CASP8、CASP9、ELANE、GPX4、GSDMD、NLRP7、NOD2、PJVK和PRKACA)为CRC患者建立了一个预后基因模型。随后基于这些基因进行了全面的生物信息学分析。ROC曲线具有良好的AUC预测价值,高危组的生存预后首先差于低危组。其次,我们发现PRGs与CRC中的炎症相关基因和免疫相关基因显著相关。然后,我们确定了PRGs与CRC中免疫浸润的相关性。例如,低危组中静息NK细胞和中性粒细胞的丰度高于高危组。
总体而言,本研究表明PRGs促进了CRC中肿瘤微环境(TME)异质性的产生。这一预后PRG模型可能为CRC的早期诊断和用药提供起点。
Pyroptosis and related gasdermin family proteins play an important role in the tumorigenesis of colorectal cancer (CRC).
However, the prognostic roles of pyroptosis-related genes (PRGs) and their relation to infiltrates of immune cells in the pathogenesis of CRC remain unclear. Using this study, we set up a prognostic gene pattern on the basis of 13 PRGs (AIM2, CASP1, CASP5, CASP6, CASP8, CASP9, ELANE, GPX4, GSDMD, NLRP7, NOD2, PJVK, and PRKACA) for CRC patients. A comprehensive bioinformatics analysis based on these genes was then performed.
With the good AUC prediction value of the ROC curves, the group with high hazard first had a poorer survival prognosis than the group with low hazard. Second, we found that PRGs were significantly related to inflammation-associated genes and immune-associated genes in CRC. Then, we identified a correlation of PRGs with immune infiltrations in CRC. For instance, the abundances of resting NK cells resting and neutrophils were higher in the low hazard group than in the high hazard group.
Overall, this work indicated that PRGs contributed to generate heterogeneity of the tumor microenvironment (TME) in CRC. This prognostic PRG model may provide a starting point for the early diagnosis and medication use of CRC.
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