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Abstract：
Glioblastoma is a highly aggressive disease with poor survival outcomes. An emerging body of literature links the role of the renin-angiotensin system (RAS), well-known for its function in the cardiovascular system, to the progression of cancers. We studied the expression of RAS-related genes (ATP6AP2, AGTR1, AGTR2, ACE, AGT, and REN) in The Cancer Genome Atlas (TCGA) glioblastoma cohort, their relationship to patient survival, and association with tumour microenvironment pathways. The expression of RAS genes was then examined in 12 patient-derived glioblastoma cell lines treated with chemoradiation. In cases of glioblastoma within the TCGA, ATP6AP2, AGTR1, ACE, and AGT had consistent expressions across samples, while AGTR2 and REN were lowly expressed. High expression of AGTR1 was independently associated with lower progression-free survival (PFS) (p = 0.01) and had a non-significant trend for overall survival (OS) after multivariate analysis (p = 0.095). The combined expression of RAS receptors (ATP6AP2, AGTR1, and AGTR2) was positively associated with gene pathways involved in hypoxia, microvasculature, stem cell plasticity, and the molecular characterisation of glioblastoma subtypes. In patient-derived glioblastoma cell lines, ATP6AP2 and AGTR1 were upregulated after chemoradiotherapy and correlated with an increase in HIF1A expression. This data suggests the RAS is correlated with changes in the tumour microenvironment and associated with glioblastoma survival outcomes.
摘要：
胶质母细胞瘤是一种高度侵袭性疾病，生存结果较差。新兴的文献将肾素-血管紧张素系统（RAS）的作用联系起来，以其在心血管系统中的功能而闻名，癌症的进展。我们研究了RAS相关基因（ATP6AP2，AGTR1，AGTR2，ACE，AGT,和REN）在癌症基因组图谱（TCGA）胶质母细胞瘤队列中，他们与病人生存的关系，以及与肿瘤微环境途径的关联。然后在经过放化疗处理的12个患者来源的胶质母细胞瘤细胞系中检查RAS基因的表达。在TCGA内的胶质母细胞瘤的情况下，ATP6AP2,AGTR1,ACE,AGT在样本中具有一致的表达式，而AGTR2和REN表达较低。AGTR1的高表达与较低的无进展生存期（PFS）独立相关（p=0.01），并且在多变量分析后，总生存期（OS）的趋势不明显（p=0.095）。RAS受体(ATP6AP2、AGTR1和AGTR2)的联合表达与参与缺氧的基因通路呈正相关,微脉管系统，干细胞可塑性，和胶质母细胞瘤亚型的分子特征。在患者来源的胶质母细胞瘤细胞系中，放化疗后ATP6AP2和AGTR1上调，并与HIF1A表达增加相关。该数据表明RAS与肿瘤微环境的变化相关，并与胶质母细胞瘤的生存结果相关。
