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文章:

探索遗传决定因素:全面分析多形性胶质母细胞瘤患者中Serpin B家族单核苷酸多态性与预后的关联

Exploring Genetic Determinants: A Comprehensive Analysis of Serpin B Family SNPs and Prognosis in Glioblastoma Multiforme Patients

原文发布日期:10 March 2024

DOI: 10.3390/cancers16061112

类型: Article

开放获取: 是

 

英文摘要:

Serpins are serine proteinase inhibitors, with several serpins being overexpressed in cancer cells. Thus, we aim to analyze the single-nucleotide polymorphism (SNP) ofSerpinb11and its association with GBM survival. A cohort of 63 GBM patients recruited from King Abdullah University Hospital in Jordan underwent polymorphism analysis and overall survival (OS) assessments. The Cancer Genome Atlas (GBM) cohort was useful for validation. We constructed a risk score using the principal component analysis for the following Serpin genes:Serpinb3, Serpinb5, Serpinb6, Serpinb11,andSerpinb12, and patients were grouped into high- vs. low-risk groups based on the median cutoff. Univariable Cox models were used to study the survival outcomes. We identified a significant association between rs4940595 and survival. In the TCGA cohort,Serpinb3alterations showed worse OS. Univariable Cox showed worse PFS outcomes with higher SERPINB5 and SERPINB6 expression. A Serpin B 5-gene risk score showed a trend towards worse PFS in the high-risk group. Upregulated DEGs showed GO enrichment in cytokine regulation and production, positive regulation of leukocyte activation, and the MAPK cascade. The high-risk group showed a significantly higher infiltration of M2 macrophages and activated mast cells. Our findings showed a significant role of the Serpin B family in GBM survival in the Jordanian population.

 

摘要翻译: 

丝氨酸蛋白酶抑制剂(Serpins)是一类丝氨酸蛋白酶抑制剂,其中多种在癌细胞中过度表达。因此,本研究旨在分析Serpinb11的单核苷酸多态性(SNP)及其与胶质母细胞瘤(GBM)患者生存期的关联。研究纳入了来自约旦阿卜杜拉国王大学医院的63例GBM患者队列,进行了多态性分析和总生存期(OS)评估。癌症基因组图谱(TCGA)的GBM队列用于验证分析。我们采用主成分分析法构建了包含以下Serpin基因的风险评分:Serpinb3、Serpinb5、Serpinb6、Serpinb11和Serpinb12,并根据中位截断值将患者分为高风险组和低风险组。采用单变量Cox模型分析生存结局。研究发现rs4940595多态位点与生存期存在显著关联。在TCGA队列中,Serpinb3基因改变显示更差的OS。单变量Cox分析表明,SERPINB5和SERPINB6高表达与更差的无进展生存期(PFS)相关。Serpin B五基因风险评分显示高风险组的PFS有恶化趋势。上调的差异表达基因在GO富集分析中显示与细胞因子调控及生成、白细胞活化正调控以及MAPK级联反应相关。高风险组中M2型巨噬细胞和活化肥大细胞的浸润显著增高。本研究结果表明,Serpin B家族在约旦人群GBM生存中具有重要作用。

 

原文链接:

Exploring Genetic Determinants: A Comprehensive Analysis of Serpin B Family SNPs and Prognosis in Glioblastoma Multiforme Patients

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