确定坏死性凋亡相关基因在较低级别胶质瘤患者中的表达及预后意义。 方法 从肿瘤基因组图谱(TCGA)数 据库中整合较低级别胶质瘤的相关临床实践数据和测序数据,并将数据库检索到的坏死性相关基因进行比较与分析。 首先 使用单变量 Cox 回归筛选出与较低级别胶质瘤患者预后相关的坏死性凋亡基因,其次采用多变量 Cox 回归筛选具有调控预后 作用的基因。 高、低风险组各 253 例,基线材料经分析无统计学差异。 通过对高、低风险组预后相关基因进行 GO 富集,以此 总结出产生可能影响风险差异的因素,随后采用 ssGSEA 剖析数据,考察高、低风险组的免疫功能状态。 结果 Lasso 回归和较 低级别胶质瘤预后使用单变量 Cox 回归鉴定了 7 个基因,且高风险组和低风险组都可以用这 7 个基因的预后风险评分模型进 行区分。 Kaplan-Meier 数据生存分析表明,低风险组的总生存率要远高于高危组。 GO 富集数据分析表明,高风险组的免疫力 与低风险组相比较,存在显著性的差异,而 ssGSEA 富集分析显示,高风险组大多数免疫细胞的评分与低风险组相比较,同样 存在显著差异,低风险组评分降低。 结论 FADD、FAS、MLKL、RIPK1、RIPK3、TLR3 和 TNF 的 7 个基因与较低级别胶质瘤患者坏死性凋亡显著相关,可作为下一步较低级别胶质瘤患者治疗的靶点。

Objective To determine the expression and prognostic significance of necrotic apoptosis-related genes in patients with lower grade gliomas. Method The clinical practice data and sequencing data of lower grade gliomas were integrated from the TCGA database and the necrosis-related genes retrieved from the database were compared and analyzed. First univariate Cox regression was used to screen the genes of necrotic apoptosis related to the prognosis of patients with lower grade glioma and then multivariate Cox regression was used to screen the genes that have the effect of regulating the prognosis. Through GO enrichment of prognostication-related genes in high and low risk groups the factors that may affect the risk difference were summarized and then the immune function status of high and low risk groups was investigated using ssGSEA analysis data. Result Seven genes were identified by Lasso regression and lower grade glioma prognosis using univariate Cox regression and the high-risk and low-risk groups could be distinguished by the prognostic risk scoring model of these seven genes. Kaplan-Meier data survival analysis showed that the overall survival rate of the low-risk group was much higher than that of the high-risk group. The GO enrichment data analysis showed that there was a significant difference in the immunity of the high - risk group compared with the low - risk group while the ssGSEA enrichment analysis showed that the scores of most immune cells in the high - risk group were also significantly different from the low-risk group and the scores of the low-risk group were lower. Conclusion The seven genes of FADD FAS MLKL RIPK1 RIPK3 TLR3 and TNF are significantly associated with necrotic apoptosis in patients with lower grade gliomas and can be used as the next target for the treatment of lower grade gliomas.