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在口腔皮细胞癌中,基于DNA甲基化的免疫微环境和与免疫相关的长非编码RNA的描绘

Naiade Calanca¹, Ana Lucia Noronha Francisco², Daniela Bizinelli³

¹Department 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.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

|September 24, 2023

概括

口腔状细胞癌 (OSCC) 呈现出显著的免疫细胞异质性. 在OSCC中异常的表观遗传特征影响免疫细胞组成和长非编码RNA表达,这表明了新的表观免疫疗法策略.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

口腔状细胞癌 (OSCC) 是一种异质性疾病.
瘤微环境和表观遗传变化影响OSCC的进展和治疗反应.
与免疫相关的长非编码RNA (lncRNAs) 与OSCC的免疫抑制微环境有关.

研究的目的:

为了研究OSCC的免疫细胞组成和表观遗传景观.
在OSCC中识别差异甲基化免疫相关的lncRNA.
在OSCC中探索表观遗传失调和免疫微环境之间的关系.

主要方法:

在46个匹配的OSCC和正常组织上进行全基因组DNA甲基化分析 (Infinium HumanMethylation450 BeadChip).
计算解卷 (MethylCIBERSORT) 来推断免疫细胞的组成.
使用癌症基因组图谱 (TCGA) 数据集分析免疫标记物和lncRNA表达的分析;通过双硫酸盐-火烧序列测试进行验证.

主要成果:

OSCC组织显示出明显的免疫细胞形状,富含单细胞系,NK,细胞毒性T细胞,调节性T细胞和中性粒细胞,但减少了B细胞,效应性T细胞和纤维细胞.
在特定的CpG位点证实了免疫相关lncRNAs (MEG3,MIR155HG,WFDC21P) 的低甲基化.
在OSCC中检测到关键免疫标记物 (例如FOXP3,GZMB,IL10,IFNG,IDO1) 的升级.

结论:

改变的免疫细胞组成和失调的免疫关联lncRNA突出显示了在OSCC中免疫微环境的关键作用.
表观遗传修饰在OSCC中显著影响免疫细胞透和功能.
针对表观遗传和免疫通路 (epi-免疫疗法) 是OSCC的有前途的治疗策略.

关键词:

通过DNA甲基化.解体解体是一种解体.在 LncRNAs 中.口腔癌是一种口腔癌.瘤的免疫微环境

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