背景:REEP4参与有丝分裂的生物学过程的调节。低级别的神经胶质瘤(LGG),作为恶性肿瘤,伴有有丝分裂异常,但是到目前为止还没有REEP4的报道。
方法:我们收集了转录组数据,DNA甲基化数据和成千上万LGG患者的临床特征。采用各种大数据分析方法和分子生物学实验来揭示REEP4对LGG病理过程的影响。
结果:发现REEP4的表达显着升高,并受到其甲基化位点的负调控。因此,REEP4的高表达和cg1631404的低甲基化状态均显示患者生存率较低。此外,REEP4高表达参与多种癌症相关细胞信号通路的调节,比如细胞周期,MAPK信号通路,NOD样受体信号通路,等。更重要的是,LGG肿瘤微环境中REEP4高表达组的免疫细胞浸润水平显著增加,且REEP4与PD-L1等免疫检查点呈高度正相关。
结论:简而言之,这项研究首次将REEP4引入恶性肿瘤中,可作为参与LGG恶性进程的独立危险因素。更重要的是,REEP4有潜力成为抗肿瘤医治范畴的一颗新星。
REEP4 is involved in the regulation of the biological process of mitosis. Lower grade glioma (LGG), as a malignant tumor, is accompanied by abnormalities in mitosis, but there have been no reports of
REEP4 so far.
We collected transcriptome data, DNA methylation data and the clinical characteristics of thousands of patients with LGG. Various big data analysis methods and molecular biology experiments were employed to reveal the impact of REEP4 on the pathological process of LGG.
It was found that the expression of
REEP4 was significantly elevated and negatively regulated by its methylation site. Therefore, both the high expression of
REEP4 and low methylation state of cg16311504 showed that the patients are correlated with lower patient survival rate. In addition, high
REEP4 expression participates in the regulation of various cancer-related cellular signaling pathways, such as the cell cycle, MAPK signaling pathway, NOD-like receptor signaling pathway, etc. More importantly, the level of immune cell infiltration significantly increased in the high expression group of REEP4 in the LGG tumor microenvironment and REEP4 has a high positive correlation with PD-L1 and other immune checkpoints.
In brief, this study is the first to introduce REEP4 in malignant tumors, which can be used as an independent risk factor that participates in the malignant process of LGG. More importantly, REEP4 has the potential to become a new star in the field of anti-tumor treatment.