We conducted a pilot study to analyze the differential methylation status of 20 primary acinar adenocarcinomas of the lungs. These adenocarcinomas had to be wild type in mutation analysis and had either high (TPS > 50%;n= 10) or negative (TPS < 1%;n= 10) PD-L1 status to be integrated into our study. To examine the methylation of 866,895 specific sites, we utilized the Illumina Infinium EPIC bead chip array. Both hypermethylation and hypomethylation play significant roles in tumor development, progression, and metastasis. They also impact the formation of the tumor microenvironment, which plays a decisive role in tumor differentiation, epigenetics, dissemination, and immune evasion. The gained methylation patterns were correlated with PD-L1 expression. Our analysis has identified distinct methylation patterns in lung adenocarcinomas with high and negative PD-L1 expression. After analyzing the correlation between the methylation results of genes and promoters with their pathobiology, we found that tumors with high expression of PD-L1 tend to exhibit oncogenic effects through hypermethylation. On the other hand, tumors with negative PD-L1 expression show loss of their suppressor functions through hypomethylation. The suppressor functions of hypermethylated genes and promoters are ineffective compared to simultaneously activated dominant oncogenic mechanisms. The tumor microenvironment supports tumor growth in both groups.
我们开展了一项初步研究，分析20例原发性肺腺泡腺癌的差异甲基化状态。这些腺癌在突变分析中需为野生型，且PD-L1状态需为高表达（TPS > 50%；n=10）或阴性（TPS < 1%；n=10）才能纳入研究。为检测866,895个特定位点的甲基化情况，我们采用Illumina Infinium EPIC甲基化芯片进行分析。高甲基化与低甲基化在肿瘤发生、进展及转移过程中均发挥重要作用，同时影响肿瘤微环境的形成，而肿瘤微环境对肿瘤分化、表观遗传调控、播散及免疫逃逸具有决定性影响。研究将获得的甲基化模式与PD-L1表达进行关联分析。结果显示，PD-L1高表达与阴性表达的肺腺癌存在显著差异的甲基化特征。通过分析基因及启动子甲基化结果与病理生物学特征的关联，我们发现PD-L1高表达肿瘤倾向于通过高甲基化机制发挥促癌效应，而PD-L1阴性肿瘤则通过低甲基化导致抑癌功能丧失。与同时激活的显性致癌机制相比，高甲基化基因及启动子的抑癌功能呈现相对无效状态。值得注意的是，两种类型的肿瘤微环境均对肿瘤生长具有支持作用。
肿瘤(癌症)患者之家