Department of Pathology, University of Yamanashi, Chuo City, Yamanashi Prefecture, Japan.
Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States of America.
PLoS One. 2023 Oct 5;18(10):e0290542. doi: 10.1371/journal.pone.0290542. eCollection 2023.
PRAME (PReferentially expressed Antigen in MElanoma) is a biomarker studied in various human cancers. Little is known about the biological implications of PRAME in glioma. We aimed to perform a comprehensive analysis to explore PRAME gene expression and its biological and clinicopathological significance in gliomas.
We accessed the human cancer atlas (TCGA) database to collect glioma patients (n = 668) with primary tumors and gene expression data. Single nucleotide variants, copy number variation, DNA methylation data, and other clinicopathological factors were also extracted for the analysis.
Overall, 170, 484, and 14 tumors showed no expression, low expression (FPKM≤1), and overexpression (FPKM>1) of the PRAME gene, respectively. The principal component analysis and pathway analyses showed that PRAME-positive gliomas (n = 498), which consisted of tumors with PRAME low expression and overexpression, expressed different oncogenic profiles, possessing higher activity of Hedgehog, P3IK-AKT-mTOR, and Wnt/β-catenin pathways (p<0.001). DNA methylation analysis also illustrated that PRAME-positive tumors were distributed more densely within a grade 4-related cluster (p<0.001). PRAME positivity was an independent prognostic factor for poor outcomes in a multivariate cox analysis adjusted for clinical characteristics and genetic events. Kaplan-Meier analysis stratified by revised classification showed that PRAME positivity was solely associated with IDH-wildtype glioblastoma, grade 4. Finally, PRAME-overexpressing cases (n = 14) had the worst clinical outcome compared to the PRAME-negative and PRAME-low cohorts (adjusted p<0.001) in pairwise comparisons.
PRAME expression statuses may dictate different biological and clinicopathological profiles in IDH-wildtype glioblastoma.
PRAME（黑色素瘤中优先表达的抗原）是一种在各种人类癌症中研究的生物标志物。关于 PRAME 在神经胶质瘤中的生物学意义知之甚少。我们旨在进行全面分析，以探索 PRAME 基因在神经胶质瘤中的表达及其生物学和临床病理意义。
我们访问了人类癌症图谱（TCGA）数据库，以收集原发性肿瘤和基因表达数据的神经胶质瘤患者（n = 668）。还提取了单核苷酸变异、拷贝数变异、DNA 甲基化数据和其他临床病理因素进行分析。
总体而言，170、484 和 14 种肿瘤分别表现出 PRAME 基因无表达、低表达（FPKM≤1）和过表达（FPKM>1）。主成分分析和途径分析表明，PRAME 阳性神经胶质瘤（n = 498）由 PRAME 低表达和过表达的肿瘤组成，表现出不同的致癌谱，具有更高的 Hedgehog、P3IK-AKT-mTOR 和 Wnt/β-catenin 途径活性（p<0.001）。DNA 甲基化分析还表明，PRAME 阳性肿瘤在 4 级相关簇中分布更为密集（p<0.001）。在调整临床特征和遗传事件的多变量 Cox 分析中，PRAME 阳性是不良预后的独立预后因素。Kaplan-Meier 分析按修订分类分层表明，PRAME 阳性仅与 IDH 野生型胶质母细胞瘤、4 级相关。最后，与 PRAME 阴性和 PRAME 低表达队列相比，PRAME 过表达病例（n = 14）在两两比较中具有最差的临床结局（调整后 p<0.001）。
PRAME 表达状态可能决定 IDH 野生型胶质母细胞瘤不同的生物学和临床病理特征。
