DataSheet_1_A four oxidative stress gene prognostic model and integrated immunity-analysis in pancreatic adenocarcinoma.docx

Background and aimsPancreatic adenocarcinoma (PAAD) is highly aggressive and characterized by a poor prognosis. Oxidative stress has great impacts on the occurrence and development of tumors. However, the predictive role of oxidative stress related genes on PAAD patients’ prognosis remains unclear. In this study, we aimed to construct a prognostic model for PAAD based on oxidative stress genes and to evaluate its predictive value.MethodsThe Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets were used to identify differentially expressed oxidative stress genes. Univariate Cox regression, Kaplan-Meier and multivariate Cox regression analysis were used to select genes and to construct a prognosis model. According to the median value of the model’s risk score, patients were divided into high and low risk groups, and gene set enrichment analysis (GSEA), immune infiltration and immunotherapy effect, drug resistance and the expression of immune checkpoint related genes and synthetic driver genes of T cell proliferation were analyzed. Finally, the mRNA and protein levels of four genes in PAAD were verified by the clinical proteomic tumor analysis consortium (CPTAC) database and the immunostaining of patients’ tissue.Results55 differentially expressed oxidative stress genes were identified, and four genes including MET, FYN, CTTN and CDK1 were selected to construct a prognosis model. GESA indicated that immune related pathways, metabolic pathways and DNA repair pathways were significantly enriched in the high risk group as compared to the low risk group. The frequency of genetic mutations was also significantly higher in high risk groups than that in low risk groups. Moreover, the infiltration level of 23 immune cells as well as the expression of immune checkpoint related and synthetic driver genes of T cell proliferation were significantly altered, with the better immunotherapy effect occurring in low risk group. In patient PAAD tissues, the mRNA and protein levels of these four genes were up-regulated.ConclusionWe have successfully constructed a four oxidative stress gene prognostic model that has important predictive value for PAAD patients, and this model might be a promising guidance for prognostic prediction and efficacy monitoring in clinical individualized therapy.

背景与目的：胰腺腺癌（PAAD）是一种高度侵袭性的疾病，其预后通常不佳。氧化应激对肿瘤的发生和发展具有重大影响。然而，氧化应激相关基因在PAAD患者预后预测中的预测作用尚不明确。本研究旨在构建基于氧化应激基因的PAAD预后模型，并评估其预测价值。
方法：本研究使用了癌症基因组图谱（TCGA）和三个基因表达综合数据库（GEO）数据集，以识别差异表达的氧化应激基因。通过单因素Cox回归、Kaplan-Meier生存分析和多因素Cox回归分析，选择了基因并构建了预后模型。根据模型风险评分的中位数，患者被分为高风险组和低风险组，并进行了基因集富集分析（GSEA）、免疫浸润和免疫治疗效应、耐药性和免疫检查点相关基因以及T细胞增殖的合成驱动基因的表达分析。最后，通过临床蛋白质组肿瘤分析联盟（CPTAC）数据库和患者组织免疫染色验证了PAAD中四个基因的mRNA和蛋白质水平。
结果：鉴定出55个差异表达的氧化应激基因，并选择了包括MET、FYN、CTTN和CDK1在内的四个基因构建预后模型。GESA显示，与低风险组相比，高风险组中免疫相关通路、代谢通路和DNA修复通路显著富集。高风险组中基因突变的频率也显著高于低风险组。此外，23种免疫细胞的浸润水平以及免疫检查点相关和T细胞增殖的合成驱动基因的表达均发生了显著改变，低风险组的免疫治疗效果更好。在患者PAAD组织中，这些四个基因的mRNA和蛋白质水平上调。
结论：本研究成功构建了一个具有重要预测价值的四氧化应激基因预后模型，该模型可能为PAAD患者的预后预测和疗效监测在临床个性化治疗中提供有前景的指导。