PDF(Pubmed)
Abstract：
UNASSIGNED: Hepatoblastoma (HB) is the most common liver tumor in children with easy metastasis. The emergence of ferroptosis as a novel form of cell death has gained increased attention in various human cancers. However, the roles of ferroptosis-related (FR) genes in HB remain elusive.
UNASSIGNED: The GSE133039, GSE131329, and GSE81928 datasets were utilized for screening core FR genes in HB. Through Lasso regression analysis and using the support vector machine recursive feature elimination (SVM-RFE) algorithm, three candidate FR genes were obtained for characterizing HB. Their expression patterns and their clinical associations were explored through the \'Limma\' R package, and their diagnostic potential was evaluated using ROC curves. Nitric oxide synthase 2 (NOS2) emerged as a candidate for further analyses. The CIBERSORT algorithm and GSEA dataset were used to respectively investigate the immune and metabolism effects of NOS2; the former was validated through immunofluorescence. The GSDC database was employed to analyze the correlation between NOS2 expression and the therapeutic efficacy of multiple drugs. PCR, Western blotting, colony formation assays, and Transwell experiments, were used to determine biological functions of NOS2 in HB cells. Potential upstream transcription factors of NOS2 were predicted through the TRRUST, hTFtarget, GeneCards, and JASPAR databases.
UNASSIGNED: NQO1, SLC1A4, and NOS2 were identified as potential genes in HB and found to be significantly upregulated in tumor samples. Nevertheless, only NOS2 was closely associated with HB clinicopathological characteristics; high NOS2 expression indicated poor prognosis, metastatic tendency, and late clinical stage. Immune analyses indicated that high NOS2 expression was concomitant with decreased infiltration levels of CD8+ T cells but increased infiltration levels of macrophages. GSEA revealed that NOS2 failed to affect the enrichments of glycolysis, fatty acid metabolism, and cholesterol biosynthesis in HB. Moreover, NOS2 was positively correlated with the IC50 values of trametinib, lapatinib, and cisplatin. NOS2 overexpression promoted the proliferation, migration and invasion of HepG2 and HuH-6 cells. JUND was identified as a potential transcriptional regulator of NOS2 by binding to its promoter (5\'-TTCTGACTCTTTT-3\').
UNASSIGNED: NOS2 plays a significant role in HB clinical assessments and holds promise as a novel therapeutic target.
UNASSIGNED: The GSE133039, GSE131329, and GSE81928 datasets were utilized for screening core FR genes in HB. Through Lasso regression analysis and using the support vector machine recursive feature elimination (SVM-RFE) algorithm, three candidate FR genes were obtained for characterizing HB. Their expression patterns and their clinical associations were explored through the \'Limma\' R package, and their diagnostic potential was evaluated using ROC curves. Nitric oxide synthase 2 (NOS2) emerged as a candidate for further analyses. The CIBERSORT algorithm and GSEA dataset were used to respectively investigate the immune and metabolism effects of NOS2; the former was validated through immunofluorescence. The GSDC database was employed to analyze the correlation between NOS2 expression and the therapeutic efficacy of multiple drugs. PCR, Western blotting, colony formation assays, and Transwell experiments, were used to determine biological functions of NOS2 in HB cells. Potential upstream transcription factors of NOS2 were predicted through the TRRUST, hTFtarget, GeneCards, and JASPAR databases.
UNASSIGNED: NQO1, SLC1A4, and NOS2 were identified as potential genes in HB and found to be significantly upregulated in tumor samples. Nevertheless, only NOS2 was closely associated with HB clinicopathological characteristics; high NOS2 expression indicated poor prognosis, metastatic tendency, and late clinical stage. Immune analyses indicated that high NOS2 expression was concomitant with decreased infiltration levels of CD8+ T cells but increased infiltration levels of macrophages. GSEA revealed that NOS2 failed to affect the enrichments of glycolysis, fatty acid metabolism, and cholesterol biosynthesis in HB. Moreover, NOS2 was positively correlated with the IC50 values of trametinib, lapatinib, and cisplatin. NOS2 overexpression promoted the proliferation, migration and invasion of HepG2 and HuH-6 cells. JUND was identified as a potential transcriptional regulator of NOS2 by binding to its promoter (5\'-TTCTGACTCTTTT-3\').
UNASSIGNED: NOS2 plays a significant role in HB clinical assessments and holds promise as a novel therapeutic target.
摘要：
■肝母细胞瘤（HB）是儿童中最常见的易转移的肝脏肿瘤。作为一种新的细胞死亡形式，铁性凋亡的出现在各种人类癌症中得到了越来越多的关注。然而,铁凋亡相关（FR）基因在HB中的作用仍然难以捉摸。
■GSE133039、GSE131329和GSE81928数据集用于筛选HB中的核心FR基因。通过Lasso回归分析,采用支持向量机递归特征消除(SVM-RFE)算法,获得了三个候选FR基因用于表征HB。通过“Limma”R包探索了它们的表达模式和临床关联，并使用ROC曲线评估其诊断潜力。一氧化氮合酶2（NOS2）成为进一步分析的候选者。使用CIBERSORT算法和GSEA数据集分别研究NOS2的免疫和代谢效应，并通过免疫荧光对前者进行验证。利用GSDC数据库分析NOS2表达与多种药物疗效的相关性。PCR,西方印迹,集落形成试验,和Transwell实验,用于确定HB细胞中NOS2的生物学功能。通过TRRUST预测NOS2的潜在上游转录因子，hTFtarget,GeneCards,和JASPAR数据库。
■NQO1，SLC1A4和NOS2被鉴定为HB中的潜在基因，并发现在肿瘤样品中显著上调。然而，只有NOS2与HB临床病理特征密切相关;NOS2高表达提示预后不良,转移倾向，和晚期临床阶段。免疫分析表明，高NOS2表达伴随着CD8T细胞浸润水平降低，但巨噬细胞浸润水平增加。GSEA揭示NOS2未能影响糖酵解的富集，脂肪酸代谢，和HB中胆固醇的生物合成。此外，NOS2与曲美替尼的IC50值呈正相关,拉帕替尼,和顺铂.NOS2过表达促进细胞增殖,HepG2和HuH-6细胞的迁移和侵袭。JUND通过结合其启动子(5'-TTCTGACTCTTTT-3')被鉴定为NOS2的潜在转录调节因子。
■NOS2在HB临床评估中起着重要作用，并有望成为新的治疗靶标。
■GSE133039、GSE131329和GSE81928数据集用于筛选HB中的核心FR基因。通过Lasso回归分析,采用支持向量机递归特征消除(SVM-RFE)算法,获得了三个候选FR基因用于表征HB。通过“Limma”R包探索了它们的表达模式和临床关联，并使用ROC曲线评估其诊断潜力。一氧化氮合酶2（NOS2）成为进一步分析的候选者。使用CIBERSORT算法和GSEA数据集分别研究NOS2的免疫和代谢效应，并通过免疫荧光对前者进行验证。利用GSDC数据库分析NOS2表达与多种药物疗效的相关性。PCR,西方印迹,集落形成试验,和Transwell实验,用于确定HB细胞中NOS2的生物学功能。通过TRRUST预测NOS2的潜在上游转录因子，hTFtarget,GeneCards,和JASPAR数据库。
■NQO1，SLC1A4和NOS2被鉴定为HB中的潜在基因，并发现在肿瘤样品中显著上调。然而，只有NOS2与HB临床病理特征密切相关;NOS2高表达提示预后不良,转移倾向，和晚期临床阶段。免疫分析表明，高NOS2表达伴随着CD8T细胞浸润水平降低，但巨噬细胞浸润水平增加。GSEA揭示NOS2未能影响糖酵解的富集，脂肪酸代谢，和HB中胆固醇的生物合成。此外，NOS2与曲美替尼的IC50值呈正相关,拉帕替尼,和顺铂.NOS2过表达促进细胞增殖,HepG2和HuH-6细胞的迁移和侵袭。JUND通过结合其启动子(5'-TTCTGACTCTTTT-3')被鉴定为NOS2的潜在转录调节因子。
■NOS2在HB临床评估中起着重要作用，并有望成为新的治疗靶标。
