Department of Basic Oncology, Dokuz Eylül University Institute of Oncology, Izmir, Turkey.
Department of Pediatric Oncology, Dokuz Eylül University Institute of Oncology, Izmir, Turkey.
J Child Neurol. 2024 Oct;39(11-12):386-394. doi: 10.1177/08830738241273431. Epub 2024 Sep 5.
The aim of study was to investigate whether CASP8 (CASPASE8) could be a biomarker for prognosis in neuroblastoma. The prognostic value of CASP8 was determined by analyzing CASP8 methylation status and gene expressions in the tumor tissues of 37 neuroblastoma patients. Bisulfite and quantitative multiplex-methylation-specific polymerase chain reaction (PCR) were used to identify the methylation status. CASP8 messenger ribonucleic acid (RNA) expression levels were determined using reverse transcriptase-quantitative PCR. CASP8 expression levels associated with prognostic value were also analyzed using the TARGET NBL (141 cases) database through PDX for Childhood Cancer Therapeutics (PCAT) and SEQC (498 cases) via the R2 platform. CASP8 methylation status was associated with risk groups, MYCN amplification, and 17q gain status. CASP8 expression was found to be statistically different between high- and low-risk neuroblastoma groups. Low expression of CASP8 was associated with MYCN amplification status. Low expression of CASP8 has shown statistically significant prognostic value through TARGET NBL and SEQC-498 data sets. CASP8 messenger RNA expressions and methylation status were associated with the MYCN amplified high-risk group in neuroblastoma. CASP8 messenger RNA expressions may be considered as a clinical prognostic marker in neuroblastoma.
本研究旨在探讨胱冬肽酶 8（CASPASE8）是否可作为神经母细胞瘤预后的生物标志物。通过分析 37 例神经母细胞瘤患者肿瘤组织中 CASP8 甲基化状态和基因表达，确定 CASP8 的预后价值。采用亚硫酸氢盐和定量多重甲基化特异性聚合酶链反应（PCR）来鉴定甲基化状态。采用逆转录定量 PCR 测定 CASP8 信使核糖核酸（RNA）的表达水平。还通过 PDX 儿童癌症治疗靶向库（TARGET NBL）（141 例）和 R2 平台的 SEQC（498 例）数据库，通过 PDX 分析与 CASP8 表达水平相关的预后价值。CASP8 甲基化状态与危险组、MYCN 扩增和 17q 增益状态相关。CAAS8 表达在高危和低危神经母细胞瘤组之间存在统计学差异。CASP8 低表达与 MYCN 扩增状态相关。通过 TARGET NBL 和 SEQC-498 数据集，CASP8 低表达显示出统计学上显著的预后价值。CASP8 mRNA 表达和甲基化状态与神经母细胞瘤中 MYCN 扩增的高危组相关。CASP8 mRNA 表达可被视为神经母细胞瘤的临床预后标志物。
