PDF(Pubmed)
Abstract：
This study determined the expression of five novel biomarker candidates in IDH wild-type glioblastoma (GBM) tissues compared to non-malign brain parenchyma, as well as their prognostic relevance for the GBM patients\' outcomes. The markers were analysed by immunohistochemistry in tumour tissues (n = 186) and healthy brain tissues (n = 54). The association with the patients\' overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier and log-rank test. The prognostic value of the markers was determined using multivariate Cox proportional hazard models. AGTRAP, DIVERSIN, cytoplasmic NEDD8 (NEDD8c) and RRM1 were significantly overexpressed in tumour tissues compared to the healthy brain, while the opposite was observed for ALKBH3. AGTRAP, ALKBH3, NEDD8c and RRM1 were significantly associated with OS in univariate analysis. AGTRAP and RRM1 were also independent prognostic factors for OS in multivariate analysis. For PFS, only AGTRAP and NEDD8c reached significance in univariate analysis. Additionally, AGTRAP was an independent prognostic factor for PFS in multivariate models. Finally, combined analysis of the markers enhanced their prognostic accuracy. The combination AGTRAP/ALKBH3 had the strongest prognostic value for the OS of GBM patients. These findings contribute to a better understanding of the GBM pathophysiology and may help identify novel therapeutic targets in this type of cancer.
摘要：
这项研究确定了与非恶性脑实质相比，IDH野生型胶质母细胞瘤（GBM）组织中五种新型生物标志物候选物的表达，以及它们与GBM患者预后的相关性。通过免疫组织化学在肿瘤组织(n=186)和健康脑组织(n=54)中分析标志物。通过Kaplan-Meier和对数秩检验评估与患者总生存期(OS)和无进展生存期(PFS)的相关性。使用多变量Cox比例风险模型确定标志物的预后价值。AGTRAP,DIVERSIN,与健康大脑相比，细胞质NEDD8（NEDD8c）和RRM1在肿瘤组织中明显过表达，而ALKBH3则相反。AGTRAP,单因素分析中ALKBH3、NEDD8c和RRM1与OS显著相关。在多因素分析中，AGTRAP和RRM1也是OS的独立预后因素。对于PFS，只有AGTRAP和NEDD8c在单因素分析中达到显著性。此外,AGTRAP是多变量模型中PFS的独立预后因素。最后,标记物的联合分析提高了其预后的准确性.AGTRAP/ALKBH3组合对GBM患者的OS具有最强的预后价值。这些发现有助于更好地理解GBM病理生理学，并可能有助于确定此类癌症的新治疗靶标。
