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
基于 DNA 甲基化的口腔鳞状细胞癌免疫微环境及免疫相关长链非编码 RNA 的描绘
英文原题：DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas.
查看英文原题
DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas.
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中文摘要
口腔鳞状细胞癌（OSCC）是一种复杂且动态的疾病，以临床病理和分子异质性为特征。细胞亚群的空间和时间异质性与癌症进展相关，并涉及预后和治疗反应。新出现的证据表明，OSCC中的异常表观遗传谱可能通过调节免疫相关长链非编码RNA（lncRNA）的表达来促进免疫抑制性肿瘤微环境。使用全基因组平台（Infinium HumanMethylation450 BeadChip）对46对匹配的OSCC和正常邻近组织样本进行了DNA甲基化分析。应用基于参考的计算去卷积（MethylCIBERSORT）推断大体样本的免疫细胞组成。使用The Cancer Genome Atlas数据集研究了编码免疫标志物和差异甲基化lncRNA的基因的表达水平。OSCC标本呈现独特的免疫细胞组成，包括单核细胞谱系细胞、NK 细胞、细胞毒性T淋巴细胞、调节性T淋巴细胞和中性粒细胞的富集。相比之下，B淋巴细胞、效应T淋巴细胞和成纤维细胞在肿瘤样本中减少。通过亚硫酸氢盐焦磷酸测序确认了三个免疫相关lncRNA（MEG3、MIR155HG和WFDC21P）在个体CpG位点的低甲基化。
此外，检测到一组免疫标志物（FOXP3、GZMB、IL10、IL2RA、TGFB、IFNG、TDO2、IDO1和HIF1A）的上调。免疫细胞组成、免疫标志物改变和免疫相关lncRNA的失调强化了免疫微环境在OSCC中的影响。这些同时发生的因素导致肿瘤异质性，表明表观免疫治疗可能是治疗OSCC的有效替代方案。
展开英文摘要原文
Oral cavity squamous cell carcinoma (OSCC) is a complex and dynamic disease characterized by clinicopathological and molecular heterogeneity. Spatial and temporal heterogeneity of cell subpopulations has been associated with cancer progression and implicated in the prognosis and therapy response. Emerging evidence indicates that aberrant epigenetic profiles in OSCC may foster an immunosuppressive tumor microenvironment by modulating the expression of immune-related long non-coding RNAs (lncRNAs). DNA methylation analysis was performed in 46 matched OSCC and normal adjacent tissue samples using a genome-wide platform (Infinium HumanMethylation450 BeadChip). Reference-based computational deconvolution (MethylCIBERSORT) was applied to infer the immune cell composition of the bulk samples. The expression levels of genes encoding immune markers and differentially methylated lncRNAs were investigated using The Cancer Genome Atlas dataset.
OSCC specimens presented distinct immune cell composition, including the enrichment of monocyte lineage cells, natural killer cells, cytotoxic T-lymphocytes, regulatory T-lymphocytes, and neutrophils. In contrast, B-lymphocytes, effector T-lymphocytes, and fibroblasts were diminished in tumor samples. The hypomethylation of three immune-associated lncRNAs (MEG3, MIR155HG, and WFDC21P) at individual CpG sites was confirmed by bisulfite-pyrosequencing.
Also, the upregulation of a set of immune markers (FOXP3, GZMB, IL10, IL2RA, TGFB, IFNG, TDO2, IDO1, and HIF1A) was detected. The immune cell composition, immune markers alteration, and dysregulation of immune-associated lncRNAs reinforce the impact of the immune microenvironment in OSCC. These concurrent factors contribute to tumor heterogeneity, suggesting that epi-immunotherapy could be an efficient alternative to treat OSCC.
论文信息
- 作者
- Calanca N、Francisco ALN、Bizinelli D、Kuasne H、Barros Filho MC、Flores BCT、Pinto CAL、Rainho CA
- 第一作者单位
- Department of Clinical Genetics, University Hospital of Southern Denmark-Vejle, Institute of Regional Health Research, University of Southern Denmark, Odense 5000, Denmark; Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-689, SP, Brazil.Denmark
- 通讯作者单位
- Department of Clinical Genetics, University Hospital of Southern Denmark-Vejle, Institute of Regional Health Research, University of Southern Denmark, Odense 5000, Denmark. Electronic address: silvia.regina.rogatto@rsyd.dk.Denmark
- 期刊
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2023 Nov
- 原文标识
- PubMed 37742611 · DOI 10.1016/j.biopha.2023.115559