Lin Jia-Zhe, Lin Nuan
Neurosurgical Department, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China.
Obstetrics & Gynecology Department, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China.
Genomics. 2021 Jan;113(1 Pt 2):767-777. doi: 10.1016/j.ygeno.2020.10.008. Epub 2020 Oct 15.
Treatment for lower-grade gliomas (LGG) has been challenging. Though emerging approaches such as immunotherapy is promising, it is still faced with immune tolerance, an obstacle that may be overcome by targeting autophagy-related (ATG) genes. After identifying three differentially expressed ATG genes (RIPK2, MUL1 and CXCR4), we constructed an ATG gene risk signature by Kaplan-Meier, univariate Cox regression, least absolute shrinkage and selection operator regression and multivariate Cox regression, followed by internal and external validation using K-M and ROC analysis. Since gene set enrichment analysis (GSEA) suggested that the signature was strongly associated with immune cell functions, CIBERSORT, LM22 matrix and Pearson correlation were further performed, showing that the risk signature was significantly correlated with immune cell infiltration and immune checkpoint genes. In conclusion, we identified and independently validated an ATG gene risk signature for LGG patients, as well as discovering its significant association with LGG immune microenvironment.
低级别胶质瘤（LGG）的治疗一直具有挑战性。尽管免疫疗法等新兴方法很有前景，但它仍然面临免疫耐受问题，而靶向自噬相关（ATG）基因可能克服这一障碍。在鉴定出三个差异表达的ATG基因（RIPK2、MUL1和CXCR4）后，我们通过Kaplan-Meier法、单变量Cox回归、最小绝对收缩和选择算子回归以及多变量Cox回归构建了一个ATG基因风险特征，随后使用K-M法和ROC分析进行内部和外部验证。由于基因集富集分析（GSEA）表明该特征与免疫细胞功能密切相关，因此进一步进行了CIBERSORT、LM22矩阵和Pearson相关性分析，结果表明风险特征与免疫细胞浸润和免疫检查点基因显著相关。总之，我们鉴定并独立验证了LGG患者的ATG基因风险特征，并发现其与LGG免疫微环境存在显著关联。
