Galardi Angela, Di Paolo Virginia, Lavarello Chiara, Russo Ida, Romanzo Antonino, Miele Evelina, Vito Rita De, Longo Daniela, Petretto Andrea, Locatelli Franco, Di Giannatale Angela
Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Core Facilities-Clinical Proteomics and Metabolomics, IRCCS, Istituto Giannina Gaslini, Genoa, Italy.
Front Oncol. 2025 Apr 24;15:1511594. doi: 10.3389/fonc.2025.1511594. eCollection 2025.
This study focuses on the proteomic analysis of cerebrospinal fluid (CSF) in a patient with stage III retinoblastoma (RB) with the aim to identify molecular changes associated with central nervous system (CNS) relapse. The child received systemic chemotherapy and intrathecal topotecan as CNS prophylaxis, along with enucleation of the left eye. After two chemotherapy cycles, CNS relapse occurred, evidenced by positive CSF findings and magnetic resonance imaging (MRI) showing leptomeningeal involvement at the anterior skull base. The child's condition deteriorated, and two months later, he died due to progressive CNS disease. The aim of the study was to analyze serial CSF samples collected at different stages of treatment, as well as a control sample, to identify differences in CSF protein expression profiles during CNS RB relapse. Using mass spectrometry, a total of 1,029 proteins were identified across all CSF samples, samples were analyzed in duplicate ensuring technical replication. An unsupervised heatmap revealed 46 differentially expressed proteins. Over-regulated proteins in CSF-RB samples were primarily involved in inflammation, extracellular matrix remodeling, epithelial mesenchymal transition initiation, migration, invasion, and cellular metabolism (PON1, RNPEP, MCAM, NEGR1, NID1, SERPINA1, FAT2, RELN, NEGR1, and SEZ6). These processes are key drivers of cancer progression and metastasis. Proteomic analysis could be valuable in identifying proteins modulated in CSF during disease progression in RB patients, offering potential for new prognostic biomarkers.
本研究聚焦于一名患有III期视网膜母细胞瘤（RB）患者的脑脊液（CSF）蛋白质组学分析，旨在识别与中枢神经系统（CNS）复发相关的分子变化。该患儿接受了全身化疗和鞘内注射拓扑替康作为CNS预防措施，同时摘除了左眼。经过两个化疗周期后，发生了CNS复发，脑脊液检查结果呈阳性以及磁共振成像（MRI）显示前颅底软脑膜受累可证实这一点。患儿病情恶化，两个月后因进行性CNS疾病死亡。本研究的目的是分析在治疗不同阶段采集的系列脑脊液样本以及一个对照样本，以识别CNS RB复发期间脑脊液蛋白质表达谱的差异。使用质谱法，在所有脑脊液样本中总共鉴定出1029种蛋白质，样本进行了重复分析以确保技术重复性。一张无监督热图显示了46种差异表达的蛋白质。CSF - RB样本中上调的蛋白质主要参与炎症、细胞外基质重塑、上皮 - 间质转化起始、迁移、侵袭和细胞代谢（对氧磷酶1、肾氨肽酶、黑色素瘤细胞黏附分子、神经生长调控蛋白1、巢蛋白1、丝氨酸蛋白酶抑制剂A1、FAT2、Reelin、神经生长调控蛋白1和SEZ6）。这些过程是癌症进展和转移的关键驱动因素。蛋白质组学分析在识别RB患者疾病进展过程中脑脊液中调节的蛋白质方面可能具有重要价值，为新的预后生物标志物提供了潜力。
