摘要
目的探讨焦亡相关基因预后模型在子宫颈癌中的预后价值,并分析预后模型与子宫颈癌免疫治疗的相关性。方法利用癌症基因组图谱(TCGA)数据库,对304例子宫颈癌组织和3例正常组织做差异分析和Cox回归模型分析,筛选出差异表达、预后相关的焦亡基因。通过最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)和Cox法构建预后模型,计算风险评分。依据风险评分的中位值,将子宫颈癌患者平均分为两组:高评分组(152例)和低评分组(152例),分析焦亡与子宫颈癌预后、免疫治疗的关联。结果在子宫颈癌组织与正常组织之间差异表达的焦亡基因中,经Cox法筛选出染色质修饰蛋白4C(chromatin-modifying protein 4C,CHMP4C)、白细胞介素1A(interleukin 1A,IL1A)、肿瘤坏死因子(tumor necrosis factor,TNF)、含核苷酸结合寡聚结构域蛋白1(nucleotide-binding oligomerization domain-containing protein 1,NDD1)、颗粒酶B(granzyme B,GZMB)和TP53基因是与子宫颈癌患者总生存期相关的预后焦亡基因(P<0.05)。根据预后基因的表达量构建预后模型,通过亚组分析、生存分析进行验证。预后模型将子宫颈癌患者分为高评分组与低评分组,以风险评分中位值为截断值评估发生子宫颈癌风险,提示高评分组的总体生存率显著低于低评分组(P<0.001)。1、3、5年预后模型的ROC曲线下面积(area under roc curve,AUC)分别为0.759、0.711和0.697,预后模型是预测子宫颈癌预后的良好指标(AUC>0.5)。在肿瘤免疫图谱(TCIA)数据库获取免疫治疗的数据,分析高、低评分组接受免疫治疗后的反应差异,发现低评分组患者较高评分组接受免疫治疗效果更好,差异有统计学意义(P=0.020)。结论CHMP4C、TNF、NDD1、GZMB、TP53焦亡相关基因与子宫颈癌预后、免疫治疗相关。
Objective To investigate the prognostic value of pyroptosis-related genes in cervical cancer and to evaluate how prognostic models relate to immunotherapy.Methods In a bioinformatics database,differential analysis and Cox regression model analysis were performed on 304 cervical cancer tissues and 3 normal tissues to identify differentially expressed and prognostically relevant pyroptosis genes.The prognostic model was buit using the least absolute shrinkage and selection operator(LASSO)and Cox to calculate the risk score.The risk score formula was developed based on the expression of the scorch gene.Patients with cervical cancer were divided into two groups on average based on their risk score median value:high scoring group(152 patients)and low scoring group(152 patients),and the association of pyroptosis with cervical cancer prognosis and immunotherapy was investigated.Results Among the differentially expressed focal death genes between cervical cancer tissues and normal tissues,chromatin-modifying protein 4C(CHMP4C),interleukin 1A(IL1A),tumor necrosis factor(TNF),nucleotide-binding oligomerization domain-containing protein 1(NDD1),granzyme B(GZMB),and TP53 gene were screened by Cox method,which are pyroptosis-related prognosis genes associated with overall survival of cervical cancer patients(P<0.05).Prognostic models were built using prognostic gene expression and validated using subgroup analysis and survival analysis.The prognostic model,which divides cervical cancer patients into high-risk and low-risk groups,allows for risk assessment and suggests that overall survival in the high-risk group is significantly lower than in the low-risk group(P<0.001).The area under the ROC curve(area under roc curve,AUC)was 0.759,0.711,and 0.697 at 1,3,and 5 years,respectively,and the prognostic model was a good predictor of prognosis(AUC>0.5).Data on immunotherapy were obtained from the cancer immunome atlas(TCIA)database in order to compare the difference in response between the high-risk and low-risk groups after receiv
作者
陈凡
朱姣姣
丁瑶瑶
秦天生
CHEN Fan;ZHU Jiaojiao;DING Yaoyao;QIN Tiansheng(Department of Gynecology,Gansu Provincial Hospital,The First Clinical Medical College of Gansu University of Chinese Medicine,Lanzhou 730000,China)
出处
《中国妇产科临床杂志》
CSCD
2023年第4期392-396,共5页
Chinese Journal of Clinical Obstetrics and Gynecology
基金
甘肃省自然科学基金(21JR1RA012)
甘肃省教育厅重大项目(LCCX2021011)。
关键词
焦亡相关基因
预后模型
子宫颈癌
pyroptosis-related genes
prognostic model
cervical cancer
