Department of Neurology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000, China.
Department of Neurology, Baoding No.1 Central Hospital, Baoding, China.
J Neurooncol. 2023 Sep;164(2):367-376. doi: 10.1007/s11060-023-04428-x. Epub 2023 Sep 1.
Leptomeningeal carcinomatosis (LC) is a rare complication of non-small cell lung cancer (NSCLC) with highly mortality. Cerebrospinal fluid (CSF) as a special kind of tumor microenvironment (TME) better represents alterations than plasma. However, the clinical value of protein profiles of exosome in CSF as liquid biopsy remains unclear.
In this study, CSF samples of NSCLC patients with (LC group) or without (NSCLC group) LC were collected and compared to patients without tumors (normal group). CSF exosomes were isolated by ultracentrifugation and protein profiles were performed by label-free proteomics. Differentially expressed proteins (DEPs) were detected by bioinformatics tools and verified by parallel reaction monitoring (PRM).
A total of 814 proteins were detected. Bioinformatics analysis revealed their shared function in the complement activation, extracellular region, and complement and coagulation cascades. Between LC and NSCLC group, 72 DEPs were found among which FN1 demonstrated the highest betweenness centrality (BC) after protein-protein interaction network analysis.
We investigated the application of label free and PRM based proteomics to detect key proteins related to LC. FN1 may serve as potential indicator to classify LC and NSCLC. Extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are important in the process of LC. These data is promising for early prediction and diagnosis of LC.
脑膜转移癌（LC）是一种罕见的非小细胞肺癌（NSCLC）并发症，死亡率极高。脑脊液（CSF）作为一种特殊的肿瘤微环境（TME），比血浆更能代表变化。然而，CSF 外泌体蛋白谱作为液体活检的临床价值仍不清楚。
本研究收集了 NSCLC 患者伴 LC（LC 组）或不伴 LC（NSCLC 组）和无肿瘤患者（正常组）的 CSF 样本，并进行了比较。CSF 外泌体通过超速离心分离，采用无标记蛋白质组学进行蛋白质谱分析。通过生物信息学工具检测差异表达蛋白（DEPs），并通过平行反应监测（PRM）进行验证。
共检测到 814 种蛋白质。生物信息学分析显示，它们在补体激活、细胞外区和补体及凝血级联中具有共同的功能。在 LC 组和 NSCLC 组之间，发现了 72 种 DEPs，其中 FN1 在蛋白质-蛋白质相互作用网络分析后表现出最高的介数中心性（BC）。
我们研究了基于无标记和 PRM 的蛋白质组学在检测与 LC 相关的关键蛋白中的应用。FN1 可能作为 LC 和 NSCLC 分类的潜在指标。细胞外基质（ECM）和上皮-间充质转化（EMT）在 LC 过程中很重要。这些数据有望用于 LC 的早期预测和诊断。
