Wang Hao, Tian Ruo-Fei, Liang Xue, Fan Jing, Duan Zi-Chuan, Fan Xin-Yu, Zhang Jia-Jia, Yao Dong-Sheng, Chen Zhi-Nan, Li Ling
Institutes of Biomedicine and Department of Cell Biology, Jinan University, Guangzhou, China.
Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China.
Front Oncol. 2023 Jan 13;12:1015042. doi: 10.3389/fonc.2022.1015042. eCollection 2022.
Pancreatic 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.
The 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.
55 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.
We 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.
胰腺腺癌（PAAD）具有高度侵袭性，预后较差。氧化应激对肿瘤的发生发展有重大影响。然而，氧化应激相关基因对PAAD患者预后的预测作用仍不清楚。在本研究中，我们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。
使用癌症基因组图谱（TCGA）和三个基因表达综合数据库（GEO）来鉴定差异表达的氧化应激基因。采用单因素Cox回归、Kaplan-Meier分析和多因素Cox回归分析来选择基因并构建预后模型。根据模型风险评分的中位数，将患者分为高风险组和低风险组，并分析基因集富集分析（GSEA）、免疫浸润与免疫治疗效果、耐药性以及免疫检查点相关基因和T细胞增殖的合成驱动基因的表达。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PAAD中四个基因的mRNA和蛋白质水平。
鉴定出55个差异表达的氧化应激基因，选择包括MET、FYN、CTTN和CDK1在内的四个基因构建预后模型。GESA表明，与低风险组相比，高风险组中免疫相关途径、代谢途径和DNA修复途径显著富集。高风险组的基因突变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基因和T细胞增殖的合成驱动基因的表达均发生显著改变，低风险组的免疫治疗效果更好。在PAAD患者组织中，这四个基因的mRNA和蛋白质水平上调。
我们成功构建了一个包含四个氧化应激基因的预后模型，该模型对PAAD患者具有重要的预测价值，可能为临床个体化治疗中的预后预测和疗效监测提供有前景的指导。
