Abstract：
OBJECTIVE: Glutathione peroxidase 1 (GPX1) is a major selenoprotein in most animal tissues, primarily expressed in the cytoplasm and mitochondria of cells and peroxidase structures of certain cells. GPX1 expression is highly correlated with carcinogenesis and disease progression. The goal of the study was to determine the association between GPX1 expression and tumor therapy, and to identify GPX1 prognostic value in various malignancies.
METHODS: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) databases were used to detect the levels of GPX1 expression in human tumor tissues and normal tissues. Indeed, correlations between GPX1 and tumor purity, tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs) were explored using the TCGA cohort. Functional and enrichment analyses were performed by the GeneMANIA database and Gene Set Enrichment Analysis (GSEA), respectively. Cox regression models and Kaplan - Meier curves were used to screen for independent risk factors and estimate brain lower-grade glioma (LGG) survival probability. The Chinese Glioma Genome Atlas (CGGA) database was used to determine whether GPX1 had a race-specific effect on overall survival (OS) in LGG. The cross-interaction between GPX1 and chemoradiotherapy on LGG OS was determined by Kaplan - Meier curves. Logistic regression models of multiplicative interactions were constructed. Furthermore, the relationship between GPX1 and LGG treatment regimens was also explored through the Genomics of Drug Sensitivity in Cancer (GDSC) database.
RESULTS: GPX1 was highly expressed in various tumors, GPX1 overexpression was significantly correlated with the poor prognosis of LGG. GPX1 was found to be an independent predictive factor for LGG in both univariate and multivariate Cox models. The nomogram showed a high predictive accuracy (C-index: 0.804, 95% CI: 0.74-0.86). In addition, GPX1 was significantly associated with TMB, MSI, and MMRs in diverse cancers. GPX1 was involved in IL6/JAK/STAT3, inflammatory response, and apoptosis signaling pathways. Besides, non-radiotherapy, chemotherapy, and low GPX1 expression were important factors affecting the better prognosis of LGG. GPX1 acted as a tumor promoter, which has taken the worst effect on LGG survival, but a multiplicative interaction of GPX1*chemoradiotherapy may improve the poor clinical outcome. GPX1 was negatively correlated with the half inhibition concentration (IC50) of temozolomide (TMZ) (Spearman = -0.44, P = 4.52 ×10-26).
CONCLUSIONS: In LGG patients, high GPX1 expression was linked to a shorter OS. The interaction between GPX1 and chemoradiotherapy exhibits a beneficial clinical effect and chemotherapy was recommended for LGG patients, especially for those with high GPX1 expression. Besides, high GPX1 expression can predict TMZ sensitivity in LGG, providing potential evidence for chemotherapy. On the whole, this study presents a wealth of biological as well as clinical significance for the roles of GPX1 in human tumors, particularly in LGG.
METHODS: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) databases were used to detect the levels of GPX1 expression in human tumor tissues and normal tissues. Indeed, correlations between GPX1 and tumor purity, tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs) were explored using the TCGA cohort. Functional and enrichment analyses were performed by the GeneMANIA database and Gene Set Enrichment Analysis (GSEA), respectively. Cox regression models and Kaplan - Meier curves were used to screen for independent risk factors and estimate brain lower-grade glioma (LGG) survival probability. The Chinese Glioma Genome Atlas (CGGA) database was used to determine whether GPX1 had a race-specific effect on overall survival (OS) in LGG. The cross-interaction between GPX1 and chemoradiotherapy on LGG OS was determined by Kaplan - Meier curves. Logistic regression models of multiplicative interactions were constructed. Furthermore, the relationship between GPX1 and LGG treatment regimens was also explored through the Genomics of Drug Sensitivity in Cancer (GDSC) database.
RESULTS: GPX1 was highly expressed in various tumors, GPX1 overexpression was significantly correlated with the poor prognosis of LGG. GPX1 was found to be an independent predictive factor for LGG in both univariate and multivariate Cox models. The nomogram showed a high predictive accuracy (C-index: 0.804, 95% CI: 0.74-0.86). In addition, GPX1 was significantly associated with TMB, MSI, and MMRs in diverse cancers. GPX1 was involved in IL6/JAK/STAT3, inflammatory response, and apoptosis signaling pathways. Besides, non-radiotherapy, chemotherapy, and low GPX1 expression were important factors affecting the better prognosis of LGG. GPX1 acted as a tumor promoter, which has taken the worst effect on LGG survival, but a multiplicative interaction of GPX1*chemoradiotherapy may improve the poor clinical outcome. GPX1 was negatively correlated with the half inhibition concentration (IC50) of temozolomide (TMZ) (Spearman = -0.44, P = 4.52 ×10-26).
CONCLUSIONS: In LGG patients, high GPX1 expression was linked to a shorter OS. The interaction between GPX1 and chemoradiotherapy exhibits a beneficial clinical effect and chemotherapy was recommended for LGG patients, especially for those with high GPX1 expression. Besides, high GPX1 expression can predict TMZ sensitivity in LGG, providing potential evidence for chemotherapy. On the whole, this study presents a wealth of biological as well as clinical significance for the roles of GPX1 in human tumors, particularly in LGG.
摘要：
目的：谷胱甘肽过氧化物酶1（GPX1）是大多数动物组织中的主要硒蛋白，主要在细胞的细胞质和线粒体以及某些细胞的过氧化物酶结构中表达。GPX1表达与癌症发生和疾病进展高度相关。该研究的目的是确定GPX1表达与肿瘤治疗之间的关联。并确定GPX1在各种恶性肿瘤中的预后价值。
方法：癌症基因组图谱（TCGA），基因型-组织表达(GTEx),和人蛋白图谱(HPA)数据库用于检测GPX1在人肿瘤组织和正常组织中的表达水平。的确,GPX1与肿瘤纯度的相关性，肿瘤突变负荷（TMB），微卫星不稳定性（MSI），使用TCGA队列探索DNA错配修复基因(MMR)。通过GeneMANIA数据库和基因集富集分析（GSEA）进行功能和富集分析，分别。Cox回归模型和Kaplan-Meier曲线用于筛选独立危险因素并估计低度脑胶质瘤（LGG）生存概率。使用中国胶质瘤基因组图谱(CGGA)数据库来确定GPX1是否对LGG中的总体存活(OS)具有种族特异性影响。通过Kaplan-Meier曲线确定GPX1与放化疗对LGGOS的交叉相互作用。构建了乘法交互作用的Logistic回归模型。此外，我们还通过癌症药物敏感性基因组学(GDSC)数据库探索了GPX1和LGG治疗方案之间的关系.
结果：GPX1在各种肿瘤中高表达，GPX1过表达与LGG的不良预后显著相关。在单变量和多变量Cox模型中，发现GPX1是LGG的独立预测因子。列线图显示出较高的预测准确性（C指数：0.804，95％CI：0.74-0.86）。此外,GPX1与TMB显著相关，MSI,和不同癌症的MMR。GPX1参与IL6/JAK/STAT3、炎症反应、和凋亡信号通路。此外,非放射治疗,化疗,GPX1低表达是影响LGG预后的重要因素。GPX1作为肿瘤的启动子，这对LGG的生存产生了最严重的影响，但GPX1*放化疗的多重交互作用可能会改善不良临床结局.GPX1与替莫唑胺的半数抑制浓度(IC50)呈负相关(Spearman=-0.44,P=4.52×10-26)。
结论：在LGG患者中，高GPX1表达与较短的OS相关。GPX1和放化疗之间的相互作用表现出有益的临床效果，LGG患者推荐化疗。特别是对于那些具有高GPX1表达。此外,GPX1的高表达可以预测LGG的TMZ敏感性，为化疗提供潜在的证据。总的来说,这项研究为GPX1在人类肿瘤中的作用提供了丰富的生物学和临床意义，尤其是LGG。
方法：癌症基因组图谱（TCGA），基因型-组织表达(GTEx),和人蛋白图谱(HPA)数据库用于检测GPX1在人肿瘤组织和正常组织中的表达水平。的确,GPX1与肿瘤纯度的相关性，肿瘤突变负荷（TMB），微卫星不稳定性（MSI），使用TCGA队列探索DNA错配修复基因(MMR)。通过GeneMANIA数据库和基因集富集分析（GSEA）进行功能和富集分析，分别。Cox回归模型和Kaplan-Meier曲线用于筛选独立危险因素并估计低度脑胶质瘤（LGG）生存概率。使用中国胶质瘤基因组图谱(CGGA)数据库来确定GPX1是否对LGG中的总体存活(OS)具有种族特异性影响。通过Kaplan-Meier曲线确定GPX1与放化疗对LGGOS的交叉相互作用。构建了乘法交互作用的Logistic回归模型。此外，我们还通过癌症药物敏感性基因组学(GDSC)数据库探索了GPX1和LGG治疗方案之间的关系.
结果：GPX1在各种肿瘤中高表达，GPX1过表达与LGG的不良预后显著相关。在单变量和多变量Cox模型中，发现GPX1是LGG的独立预测因子。列线图显示出较高的预测准确性（C指数：0.804，95％CI：0.74-0.86）。此外,GPX1与TMB显著相关，MSI,和不同癌症的MMR。GPX1参与IL6/JAK/STAT3、炎症反应、和凋亡信号通路。此外,非放射治疗,化疗,GPX1低表达是影响LGG预后的重要因素。GPX1作为肿瘤的启动子，这对LGG的生存产生了最严重的影响，但GPX1*放化疗的多重交互作用可能会改善不良临床结局.GPX1与替莫唑胺的半数抑制浓度(IC50)呈负相关(Spearman=-0.44,P=4.52×10-26)。
结论：在LGG患者中，高GPX1表达与较短的OS相关。GPX1和放化疗之间的相互作用表现出有益的临床效果，LGG患者推荐化疗。特别是对于那些具有高GPX1表达。此外,GPX1的高表达可以预测LGG的TMZ敏感性，为化疗提供潜在的证据。总的来说,这项研究为GPX1在人类肿瘤中的作用提供了丰富的生物学和临床意义，尤其是LGG。
