HER2阳性乳腺癌铁死亡相关基因分析及预后预测模型的建立

Analysis of Genes Related to Ferroptosis in HER2-positive Breast Cancer and Establishment of Prognosis Prediction Model

目的筛选影响人表皮生长因子受体2(HER2)阳性乳腺癌预后的铁死亡相关基因,并构建预测模型。方法从癌症基因组图谱数据库收集乳腺癌患者肿瘤组织RNA-seq数据和临床资料,其中HER2阳性乳腺癌185例,HER2阴性乳腺癌769例。根据HER2阳性和HER2阴性乳腺癌铁死亡相关基因表达差异确定候选基因。比较不同铁死亡相关基因表达水平HER2阳性乳腺癌的生存差异。应用Pearson相关性分析铁死亡相关基因的免疫相关性。通过Cox和LASSO回归分析,根据中位风险评分将HER2阳性乳腺癌患者分为高风险组和低风险组,建立预后预测模型,并检验预测效能。结果铁死亡基因FANCD2、TFRC、ATP5MC3、CS和NFE2L2不同表达水平HER2阳性乳腺癌患者生存率比较差异有统计学意义(P<0.05),其基因表达水平越高患者预后越差。上述5个铁死亡相关基因与免疫细胞存在相关性,其中CS与CD4+T细胞存在最明显正相关,CS与NK细胞和NFE2L2与无特征细胞存在最明显负相关(P<0.01)。HER2阳性乳腺癌高风险组的生存率明显低于低风险组(P<0.05)。预后预测模型对HER2阳性乳腺癌患者治疗后3、5、8年预后预测的曲线下面积分别为0.776、0.844、0.853。结论铁死亡相关基因FANCD2、TFRC、ATP5MC3、CS和NFE2L2与HER2阳性乳腺癌患者预后具有相关性,并且建立了预后预测模型,可有效预测HER2阳性乳腺癌患者的预后。

Objective To screen ferroptosis related genes that influence the prognosis of human epidermal growth factor receptor 2(HER2)positive breast cancer,and to construct prognosis prediction models.Methods RNA-seq data and clinical data of breast cancer tissues in breast cancer patients were collected from the Cancer Genome Atlas database,including 185 HER2-positive breast cancers and 769 HER2-negative breast cancers.Candidate genes were identified based on differences in the expression of genes associated with ferroptosis in HER2-positive and HER2-negative breast cancers.The survival difference of HER2-positive breast cancer with different ferroptosis related gene expression levels was compared.The immune correlation of ferroptosis related genes was analyzed by Pearson correlation analysis.After Cox and LASSO regression analysis,patients with HER2-positive breast cancer were divided into high risk group and low risk group according to the median risk score,the prognosis prediction model was established and the prediction effectiveness was tested.Results There were significant differences in the survival rate of HER2-positive breast cancer patients with different expression levels of ferroptosis genes FANCD2,TFRC,ATP5MC3,CS and NFE2L2(P<0.05).The higher the expression level of ferroptosis genes,the worse the prognosis of patients.The above five ferroptosis related genes were correlated with immune cells,among which CS had the most significant positive correlation with CD4+T cells,and CS had the most significant negative correlation with NK cells,NFE2L2 and featurelle cells(P<0.01).The survival rate of high risk HER2-positive breast cancer group was significantly lower than that of low risk group(P<0.05).The area under the curve of prognosis prediction model for HER2-positive breast cancer patients at 3,5 and 8 years after treatment was 0.776,0.844 and 0.853,respectively.Conclusion Ferroptosis related genes FANCD2,TFRC,ATP5MC3,CS and NFE2L2 are correlated with the prognosis of HER2-positive breast cancer patients,and a prognosis prediction model has been established to effectively predict the prognosis of HER2-positive breast cancer patients.