CSF 蛋白质组生物标志物的靶向多重验证：对 PCNSL 与无肿瘤对照和其他脑肿瘤的区分的影响。
Targeted multiplex validation of CSF proteomic biomarkers: implications for differentiation of PCNSL from tumor-free controls and other brain tumors.
发表日期：2024
作者：
Jingjing Ma, Zhiguang Lin, Yaqi Zhang, Yun Ding, Qiming Tang, Yufeng Qian, Bo Jin, Ruben Y Luo, Wei-Li Liao, Sheeno Thyparambil, Zhi Han, C James Chou, James Schilling, Qing Li, Mengxue Zhang, Yunan Lin, Yan Ma, Karl G Sylvester, Seema Nagpal, Doff B McElhinney, Xuefeng B Ling, Bobin Chen
来源：
Frontiers in Immunology
摘要：
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，会影响脑实质、眼睛、脑脊液和脊髓。诊断 PCNSL 可能具有挑战性，因为影像学研究通常显示与其他脑肿瘤相似的模式，并且立体定向脑病变活检构象是侵入性的，并不总是可行。本研究旨在验证之前的脑脊液 (CSF) 蛋白质组学分析 (PMID: 32610669)，并开发基于 CSF 的蛋白质组学组合，以实现准确的 PCNSL 诊断和鉴别。CSF 样本采集自 30 例 PCNSL、30 例其他脑肿瘤、和 31 个无肿瘤/良性对照。采用液相色谱串联质谱靶向蛋白质组学分析建立基于脑脊液的蛋白质组学组合。最终的蛋白质组学组合经过选择和优化，用于诊断无肿瘤对照或其他脑肿瘤病变的 PCNSL，曲线下面积 (AUC) 为 0.873 (95%CI: 0.723-0.948) 和 0.937 (95%CI: 0.807-0.985)。通路分析显示，诊断组特征在与细胞外基质-受体相互作用、粘着斑和 PI3K-Akt 信号传导相关的通路中显着富集，而朊病毒病、矿物质吸收和 HIF-1 信号传导在分化组特征中显着富集。这项研究表明利用基于脑脊液的蛋白质组学特征进行 PCNSL 诊断和鉴别的准确临床测试组，这可能有助于克服当前诊断方法的挑战并改善患者的治疗结果。版权所有 © 2024 Ma、Lin、Zhang、Ding、Tang、Qian、Jin、Luo 、廖、Thyparambil、Han、Chou、Schilling、Li、Zhang、Lin、Ma、Sylvester、Nagpal、McElhinney、Ling 和 Chen。
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.Copyright © 2024 Ma, Lin, Zhang, Ding, Tang, Qian, Jin, Luo, Liao, Thyparambil, Han, Chou, Schilling, Li, Zhang, Lin, Ma, Sylvester, Nagpal, McElhinney, Ling and Chen.