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
SOX 家族失调与 DNA 甲基化及免疫微环境特征相关并预测肝细胞癌预后
英文原题：The Dysregulation of SOX Family Correlates with DNA Methylation and Immune Microenvironment Characteristics to Predict Prognosis in Hepatocellular Carcinoma.
查看英文原题
The Dysregulation of SOX Family Correlates with DNA Methylation and Immune Microenvironment Characteristics to Predict Prognosis in Hepatocellular Carcinoma.
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研究概要
SOX 家族基因可预测 HCC 的预后。
中文摘要
背景
肝细胞癌（HCC）存在分子异质性，多数患者对多种治疗应答不佳。本研究拟全面分析SOX基因家族在HCC中的作用，以寻找更多治疗靶点和生物标志物，为HCC治疗提供新思路。
方法
使用UALCAN、Kaplan-Meier Plotter、cBioPortal、STRING、WebGestalt、Metascape、TIMER 2.0、DiseaseMeth、MethSurv、HPA、CCLE数据库及Cytoscape软件，对生物信息学数据进行综合分析。
结果
SOX2、SOX4、SOX8、SOX10、SOX11、SOX12、SOX17和SOX18在HCC与正常组织中的表达存在显著差异，并对HCC患者分级和生存具有预测价值。SOX家族基因改变较为常见，其中SOX4和SOX17突变率最高。SOX家族可能主要通过调节血管生成相关信号通路影响HCC。SOX4、SOX8、SOX11、SOX12、SOX17和SOX18与8类免疫细胞相关，包括CD8阳性T细胞、CD4阳性T细胞、B细胞、调节性T细胞、中性粒细胞、巨噬细胞、髓系树突状细胞和NK细胞；多数免疫细胞与SOX家族呈正相关。值得注意的是，CD4阳性T细胞和巨噬细胞与所有上述SOX家族成员均呈正相关，而NK细胞与多数SOX家族基因呈负相关。与正常组织相比，HCC中SOX2、SOX4和SOX10启动子区域DNA甲基化水平较低，而SOX8、SOX11、SOX17和SOX18甲基化水平较高。此外，SOX12和SOX18较高的DNA甲基化水平与HCC患者较差生存相关。
结论
SOX家族基因可用于预测HCC预后；血管生成相关信号通路调控可能参与HCC进展。DNA甲基化水平和免疫微环境特征，尤其是CD4阳性T细胞及巨噬细胞浸润，可能为HCC预后预测提供新视角。
展开英文摘要原文
BACKGROUND
Due to the molecular heterogeneity of hepatocellular carcinoma (HCC), majority of patients respond poorly among various of therapy. This study is aimed at conducting a comprehensive analysis about roles of SOX family in HCC for obtaining more therapeutic targets and biomarkers which may bring new ideas for the treatment of HCC.
METHODS
UALCAN, Kaplan Meier plotter, cBioPortal, STRING, WebGestalt, Metascape, TIMER 2.0, DiseaseMeth, MethSurv, HPA, CCLE database, and Cytoscape software were used to comprehensively analyze the bioinformatic data.
RESULTS
SOX2, SOX4, SOX8, SOX10, SOX11, SOX12, SOX17, and SOX18 were significantly differentially expressed in HCC and normal tissues and were valuable for the grade and survival of HCC patients. In addition, the gene alterations of SOX family happened frequently, and SOX4 and SOX17 had the highest mutation rate. The function of SOX family on HCC may be closely correlated with the regulation of angiogenesis-related signaling pathways. Moreover, SOX4, SOX8, SOX11, SOX12, SOX17, and SOX18 were correlation with 8 types of immune cells (including CD8+ T cell, CD4+ T cell, B cell, Tregs, neutrophil, macrophage, myeloid DC, and NK cell), and we found that most types of immune cells had a positive correlation with SOX family. Notably, CD4+ T cell and macrophage were positively related with all these SOX family. NK cells were negatively related with most SOX family genes. DNA methylation levels in promoter area of SOX2, SOX4, and SOX10 were lower in HCC than normal tissues, while SOX8, SOX11, SOX17, and SOX18 had higher DNA methylation levels than normal tissues. Moreover, higher DNA methylation level of SOX12 and SOX18 demonstrated worse survival rates in patients with HCC.
CONCLUSION
SOX family genes could predict the prognosis of HCC. In addition, the regulation of angiogenesis-related signaling pathways may participate in the development of HCC. DNA methylation level and immune microenvironment characteristics (especially CD4+ T cell and macrophage immune cell infiltration) could be a novel insight for predicting prognosis in HCC.
论文信息
- 作者
- Qin S、Liu G、Jin H、Chen X、He J、Xiao J、Qin Y、Mao Y
- 单位
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China; and Department of Pathology, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.China
- 期刊
- Disease markers2022
- 原文标识
- PubMed 35465267 · DOI 10.1155/2022/2676114
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