Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.
College of Automation, Guangdong Polytechnic Normal University, Guangzhou, China.
Front Immunol. 2024 Aug 1;15:1343109. doi: 10.3389/fimmu.2024.1343109. eCollection 2024.
Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation.
CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels.
Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features.
This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.
原发性中枢神经系统淋巴瘤（PCNSL）是一种罕见的非霍奇金淋巴瘤，影响脑实质、眼睛、脑脊液和脊髓。诊断 PCNSL 具有挑战性，因为影像学研究通常显示出与其他脑瘤相似的模式，而立体定向脑病变活检确认具有侵入性，并非总是可行。本研究旨在验证先前脑脊液（CSF）的蛋白质组学分析（PMID：32610669），并开发基于 CSF 的蛋白质组学面板，以实现准确的 PCNSL 诊断和鉴别。
从 30 例 PCNSL 患者、30 例其他脑瘤患者和 31 例无肿瘤/良性对照患者中收集 CSF 样本。采用液相色谱串联质谱靶向蛋白质组学分析建立基于 CSF 的蛋白质组学面板。
最终的蛋白质组学面板被选择和优化，以从无肿瘤对照或其他脑瘤病变中诊断 PCNSL，其曲线下面积（AUC）分别为 0.873（95%CI：0.723-0.948）和 0.937（95%CI：0.807-0.985）。通路分析表明，诊断面板特征在与细胞外基质-受体相互作用、焦点黏附和 PI3K-Akt 信号通路相关的通路中显著富集，而朊病毒病、矿物质吸收和 HIF-1 信号通路在分化面板特征中显著富集。
本研究提出了一种基于 CSF 蛋白质组学特征的 PCNSL 诊断和鉴别准确的临床检测面板，这可能有助于克服当前诊断方法的挑战，改善患者的预后。
