双硫死亡相关基因与胰腺癌预后及免疫治疗的关系探索:基于生物信息学分析

Relation between disulfidptosis-related genes and prognosis or immunotherapy of pancreatic cancer:based on bioinformatics analysis

目的 探讨双硫死亡相关基因(disulfidptosis-related genes,DRGs)与胰腺癌患者预后及免疫治疗反应的关系。方法 从癌症基因组图谱中下载胰腺癌患者的转录组数据、体细胞突变数据及对应的临床信息,从已知的15个DRGs中筛选出在胰腺癌中发生突变的DRGs,通过共识聚类算法识别出DRGs亚型,然后分析识别出的DRGs亚型与胰腺癌患者预后、免疫细胞浸润和功能富集通路的关系,进一步根据DRGs基因表达量进行风险评分并根据风险评分的均值将患者分为高风险(≥均值)和低风险(<均值)组,比较DRGs不同亚型患者的风险评分及总生存情况,同时评估风险评分与患者预后及肿瘤突变负荷的关系。结果 从癌症基因组图谱中下载了177例胰腺癌患者的转录组数据和对应的临床信息,其中有161例含有体细胞突变数据,共筛选出10个DRGs在胰腺癌中发生突变,共识聚类算法识别出2个DRGs亚型即A亚型和B亚型。A亚型胰腺癌患者的总生存情况优于B亚型胰腺癌患者(χ^(2)=8.316,P=0.003),A亚型胰腺癌患者具有更高的免疫细胞浸润丰度,在代谢和传导相关通路上显著富集。177例胰腺癌患者样本的风险评分均值为1.921,其中高风险组157例、低风险组20例,B亚型患者的风险评分高于A亚型(t=14.031,P<0.001),低风险组的总生存情况优于高风险组(χ^(2)=17.058,P<0.001),高风险胰腺癌患者的TMB值较低风险胰腺癌患者更高(t=5.642,P=0.014);161例含有体细胞突变数据患者的TMB均值为2.767,其中高TMB组128例、低TMB组33例,高TMB组患者的总生存情况较低TMB组患者差(χ^(2)=7.425,P=0.006)。结论 DRGs与胰腺癌患者的预后及免疫治疗反应有关,对DRGs展开针对性靶点治疗可能为胰腺癌的诊疗提供一种新的思路。

Objective To investigate the relation between disulfidptosis-related genes(DRGs)and prognosis or immunotherapy response of patients with pancreatic cancer(PC).Methods The transcriptome data,somatic mutation data,and corresponding clinical information of the patients with PC in The Cancer Genome Atlas(TCGA)were downloaded.The DRGs mutated in the PC were screened out from the 15 known DRGs.The DRGs subtypes were identified by consensus clustering algorithm,and then the relation between the identified DRGs subtypes and the prognosis of patients with PC,immune cell infiltration or functional enrichment pathway was analyzed.Further,a risk score was calculated according to the DRGs gene expression level,and the patients were categorized into high-risk and low-risk groups based on the mean value of the risk score.The risk score and overall survival of the patients with high-risk and low-risk were compared.Finally,the relation between the risk score and(or)tumor mutation burden(TMB)and the prognosis of patients with PC was assessed.Results The transcriptome data and corresponding clinical information of the 177 patients with PC were downloaded from TCGA,including 161 patients with somatic mutation data.A total of 10 mutated DRGs were screened out.Two DRGs subtypes were identified,namely subtype A and subtype B.The overall survival of PC patients with subtype A was better than that of patients with subtype B(χ^(2)=8.316,P=0.003).The abundance of immune cell infiltration in the PC patients with subtype A was higher and mainly enriched in the metabolic and conduction related pathways as compaired with the patients with subtype B.The mean risk score of 177 patients with PC was 1.921,including 157 cases in the high-risk group and 20 cases in the low-risk group.The risk score of patients with subtype B was higher than that of patients with subtype A(t=14.031,P<0.001).The overall survival of the low-risk group was better than that of the high-risk group(χ^(2)=17.058,P<0.001),and the TMB value of the PC patients with high-risk was higher than that of the PC patients with low-risk(t=5.642,P=0.014).The mean TMB of 161 patients with somatic mutation data was 2.767,including 128 cases in the high-TMB group and 33 cases in the low-TMB group.The overall survival of patients in the high-TMB group was worse than that of patients in the low-TMB group(χ^(2)=7.425,P=0.006).Conclusion DRGs are closely related to the prognosis and immunotherapy response of patients with PC,and targeted treatment of DRGs might potentially provide a new idea for the diagnosis and treatment of PC.