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• W4283661159 abstract "Renal cell carcinoma (RCC) is a renal cortical tumor with high clinical incidence. The effect of glutathione peroxidases (GPXs) on RCC and the possible mechanism are still unclear. This study aims to explore the expression level of GPXs gene in RCC and its effect on the clinical prognosis of patients with RCC via bioinformatics analysis.The mRNA expressions of GPXs family genes were obtained from the public data of The Cancer Genome Atlas (TCGA) database. The Kruskal-Wails test was used to analyze the differences in mRNA expression of GPXs family genes between samples from patients with RCC and the normal population. UALAN databases were used to analyze the differences in protein expression of GPXs family genes between samples from patients with renal clear cell carcinoma and the normal population, and to evaluate the role of GPXs family genes in RCC. The Kaplan-Meier Plotter was used to analyze the correlation between different types of RCC and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Kaplan-Meier survival curve was drawn based on the GPX8 gene expression to study the relationship between GPX8 gene expression and prognosis of RCC patients. Based on the results of multivariate Cox regression analysis, a Nomogram scoring model for RCC prediction was established by introducing GPX8 gene.The mRNA expressions of GPX1 and GPX4 were higher in the sample of renal chromophobe cell carcinoma, renal clear cell carcinoma, and renal papillary cell carcinoma than those in the normal population (all P<0.01), and GPX7 and GPX8 were significantly over-expressed in patients with renal papillary cell carcinoma and renal clear cell carcinoma (all P<0.01). Compared with the normal group, the protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in renal clear cell carcinoma (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). The protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in patients with renal clear cell carcinoma at different tumor grades (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). Survival analysis showed that OS, DFS, DSS, and PFS were all decreased in patients with clear cell carcinoma compared with patients with papillary cell carcinoma and chromophobe cell carcinoma. According to the GPX8 level, patients were assigned into the low, medium, and high expression groups. Compared with the low GPX8 level group, the OS (P<0.01), DFS (P=0.03), DSS (P<0.01), and PFS (P=3.18×10-7) were significantly decreased in the high level group. Univariate Cox proportional regression analysis showed that the high level of GPX8 was associated with poor OS of 3 different types of renal cancer. Multifactorial analysis showed that GPX8 was an independent factor affecting the OS of patients with renal papillary cell carcinoma. Race and post tumor node metastasis (pTNM) typing were independent factors influencing the OS of patients with renal clear cell carcinoma. GPX8 and pTMN were independent factors influencing the OS of patients with renal chromophobe cell carcinoma. Based on these variables, the Nomogram risk models of 3 types of cell carcinoma were established, and the discrimination and calibration of the models were evaluated using the Consistency index (C-index) and calibration curves. The C-index of the risk model of renal papillary cell carcinoma was 0.62 (95% CI 0.51 to 1.00, P=0.03). The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) was 0.88. The C-index of the risk model of renal clear cell carcinoma was 0.72 (95% CI 0.52 to 1.00, P=0.03). The results of ROC curve showed that the AUC was 0.90. The C-index of the risk model of chromophobe cell carcinoma of kidney was 0.90 (95% CI 0.85 to 1.00, P<0.01). The results of ROC curve showed that the AUC was 0.59.GPXs family genes, especially GPX8, are potential markers for poor prognosis of RCC, and the occurrence and development of RCC can be predicted in clinical practice based on the expressions of GPXs family genes.目的: 肾细胞癌(renal cell carcinoma，RCC)是临床高发的肾皮质肿瘤，谷胱甘肽过氧化物酶(glutathione peroxidases，GPXs)基因对RCC的影响及作用机制尚不清楚。本研究旨在通过生物信息学分析探讨GPXs基因在RCC中的表达水平及其对患者预后的影响。方法: 下载癌症基因组图谱(The Cancer Genome Atlas，TCGA)数据库的公开数据，获取GPXs家族基因mRNA表达数据，采用非参数检验-K多个独立样本检验(Kruskal-Wallis检验)分析RCC患者和正常人群样本中GPXs家族基因的mRNA表达差异；利用UALCAN数据库分析肾透明细胞癌不同患者特征样本与正常人群样本中GPXs家族基因的蛋白质表达差异，评估GPXs家族基因在RCC中的作用；采用Kaplan-Meier Plotter在线分析不同类型RCC与总生存期(overall survival，OS)、无疾病生存期(disease-free survival，DFS)、疾病特异性生存期(disease-specific survival，DSS)和无进展生存期(progression-free survival，PFS)的关系，根据GPX8基因表达水平绘制Kaplan-Meier生存曲线进一步研究GPX8基因表达水平与RCC患者预后的关系，基于多因素Cox回归分析结果，引入筛选的GPX8基因建立RCC的Nomogram列线图预测评分模型。结果: GPXs家族中GPX1、GPX4 mRNA在肾嫌色细胞癌、肾透明细胞癌和肾乳头状细胞癌患者中均显著高表达(均P<0.01)，GPX7和GPX8在肾乳头状细胞癌和肾透明细胞癌患者中均显著高表达(均P<0.01)；与正常人群组相比，肾透明细胞癌人群样本GPX1、GPX2、GPX7、GPX8的蛋白质表达水平均显著升高(均P<0.01)，GPX3、GPX4的蛋白质表达均显著降低(均P<0.01)，在肾透明细胞癌不同肿瘤分级患者样本中GPX1、GPX2、GPX7、GPX8的蛋白质表达水平均显著提高(均P<0.01)，GPX3、GPX4的蛋白质表达均显著降低(均P<0.01)。生存分析结果显示：与肾乳头细胞癌和肾嫌色细胞癌相比，肾透明细胞癌患者的OS、DFS、DSS和PFS均缩短；根据GPX8的表达水平将患者分为低、中、高表达组，与GPX8低表达组相比，高表达组RCC患者OS(P<0.01)、DFS(P=0.03)、DDS(P<0.01)和PFS(P=3.18×10-7)均显著缩短；单因素Cox比例回归分析显示GPX8高表达与3种类型RCC的不良OS相关；多因素分析显示GPX8是影响肾乳头状细胞癌患者OS的独立因素，种族、肿瘤原发灶淋巴结远处转移(post tumor node metastasis，pTNM)分型是影响肾透明细胞癌OS的独立因素，GPX8、pTNM分型是影响肾嫌色细胞癌患者OS的独立因素。构建3种类型细胞癌患者OS列线图风险模型，采用一致性指数(consistency index，C-index)和校准曲线对模型的判别和校准进行评价，肾乳头状细胞癌患者列线图风险模型C-index为0.62(95% CI：0.51~1.00，P=0.03)，受试者工作特征(receiver operating characteristic，ROC)曲线分析结果显示曲线下面积(area under the curve，AUC)为0.88。肾透明细胞癌患者列线图风险模型C-index为0.72 (95%CI：0.52~1.00，P=0.03)，AUC为0.90。肾嫌色细胞癌患者列线图风险模型C-index为0.90(95% CI：0.85~1.00，P<0.01)，AUC为0.59。结论: GPXs家族基因特别是GPX8是RCC不良预后的潜在标志物，可通过GPXs家族基因的表达情况在临床实践中预测RCC的发生和发展。." @default.
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• W4283661159 date "2022-05-28" @default.
• W4283661159 modified "2023-10-17" @default.
• W4283661159 title "Glutathione peroxidase family and survival prognosis in patients with renal cell carcinoma." @default.
• W4283661159 doi "https://doi.org/10.11817/j.issn.1672-7347.2022.210418" @default.
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