DLL3表达和甲基化与低级别胶质瘤的免疫微环境及预后相关。
DLL3 expression and methylation are associated with lower-grade glioma immune microenvironment and prognosis.
作者信息
Noor Humaira, Whittaker Shane, McDonald Kerrie L
机构信息
Cure Brain Cancer Biomarkers and Translational Research Group, Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales 2031, Australia; Adult Cancer Program, Lowy Cancer Research Centre, UNSW Sydney, Randwick, NSW 2031, Australia.
Cure Brain Cancer Biomarkers and Translational Research Group, Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales 2031, Australia; Adult Cancer Program, Lowy Cancer Research Centre, UNSW Sydney, Randwick, NSW 2031, Australia; Platelet, Thrombosis and Cancer Research Lab, ANZAC Research Institute, New South Wales 2031, Australia.
出版信息
Genomics. 2022 Mar;114(2):110289. doi: 10.1016/j.ygeno.2022.110289. Epub 2022 Feb 4.
Notch signalling pathway, particularly its ligand delta-ligand 3 (DLL3), is important in glioma, however, little is known about DLL3 regulation and prognostic effects. Immunohistochemistry on a cohort of 163 gliomas revealed DLL3 upregulation in IDH1 mutant gliomas, where it was associated with a favourable prognosis (HR[95% CI]: 0.28[0.09-0.87]; p = 0.021). We investigated the epigenetic regulation of DLL3, and identified individual CpG sites correlating with DLL3 mRNA expression, which were significant prognostic markers in LGG. In silico analysis revealed that infiltrating immune cells significantly correlated with DLL3 expression, methylation and somatic copy number alterations. The prognostic effects of DLL3 expression was significantly affected by infiltration of immune cells. RNA Sequencing of 83 LGGs and GO Term analysis of differentially expressed genes showed that low DLL3 expression was related to ciliogenesis, which was confirmed by TCGA LGG analysis. Thus, DLL3 may play an important role in the immune microenvironment and prognosis of LGGs.
Notch信号通路，尤其是其配体δ-配体3（DLL3），在胶质瘤中很重要，然而，关于DLL3的调控和预后影响知之甚少。对163例胶质瘤队列进行的免疫组织化学分析显示，DLL3在异柠檬酸脱氢酶1（IDH1）突变型胶质瘤中上调，且与良好预后相关（风险比[95%置信区间]：0.28[0.09 - 0.87]；p = 0.021）。我们研究了DLL3的表观遗传调控，并确定了与DLL3 mRNA表达相关的单个CpG位点，这些位点是低级别胶质瘤（LGG）中的显著预后标志物。计算机分析显示，浸润性免疫细胞与DLL3表达、甲基化和体细胞拷贝数改变显著相关。免疫细胞浸润显著影响DLL3表达的预后作用。对83例LGG进行的RNA测序和差异表达基因的基因本体（GO）术语分析表明，低DLL3表达与纤毛发生有关，这在癌症基因组图谱（TCGA）的LGG分析中得到了证实。因此，DLL3可能在LGG的免疫微环境和预后中发挥重要作用。
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