State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, 151# Yanjiang Road, Guangzhou, 510120, China.
Department of Neurology, Psychological and Neurological Diseases Research Centre, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.
J Neurol. 2022 Feb;269(2):815-823. doi: 10.1007/s00415-021-10660-0. Epub 2021 Jul 20.
Brain metastases (BM) remains the most cumbersome disease burden in patients with lung cancer. This study aimed to investigate whether serum brain injury biomarkers can indicate BM, to further establish related diagnostic models, or to predict prognosis of BM.
This was a prospective study of patients diagnosed with lung cancer with BM (BM group), with lung cancer without BM (NBM group), and healthy participants (control group). Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were detected at baseline. We identified and integrated the risk factors of BM to establish diagnostic models.
A total of 158 patients were included (n = 37, 57, and 64 in the BM, NBM, and control groups, respectively). Serum biomarker levels were significantly higher in the NBM group than in the control group. Higher serum NfL and GFAP concentrations were associated with BM (odds ratios, 3.06 and 1.79, respectively). NfL (area under curve [AUC] = 0.77, p < 0.001) and GFAP (AUC = 0.64, p = 0.02) had diagnostic value for BM. The final diagnostic model included NfL level, age, Karnofsky Performance Status. The model had an AUC value of 0.83 (95% confidence interval [CI] 0.75-0.92). High NfL concentration was correlated with poor overall survival of patients with BM (hazard ratio, 3.31; 95% CI 1.22-9.04; p = 0.019).
Serum NfL and GFAP could be potential diagnostic biomarkers for BM in patients with lung cancer. We established a model that can provide individual diagnoses of BM. Higher NfL level may be associated with poor prognosis of patients with BM.
脑转移（BM）仍然是肺癌患者最棘手的疾病负担。本研究旨在探讨血清脑损伤生物标志物是否可以提示 BM，进一步建立相关诊断模型，或预测 BM 的预后。
这是一项对诊断为 BM 的肺癌患者（BM 组）、无 BM 的肺癌患者（NBM 组）和健康参与者（对照组）的前瞻性研究。在基线时检测血清神经丝轻链（NfL）和神经胶质纤维酸性蛋白（GFAP）。我们确定并整合了 BM 的危险因素，以建立诊断模型。
共纳入 158 例患者（n=37、57 和 64 例分别在 BM、NBM 和对照组）。NBM 组血清生物标志物水平明显高于对照组。较高的血清 NfL 和 GFAP 浓度与 BM 相关（优势比分别为 3.06 和 1.79）。NfL（曲线下面积[AUC] = 0.77，p < 0.001）和 GFAP（AUC = 0.64，p = 0.02）对 BM 具有诊断价值。最终的诊断模型包括 NfL 水平、年龄、卡氏功能状态评分。该模型的 AUC 值为 0.83（95%置信区间 [CI] 0.75-0.92）。高 NfL 浓度与 BM 患者的总体生存不良相关（危险比，3.31；95%CI 1.22-9.04；p = 0.019）。
血清 NfL 和 GFAP 可能是肺癌患者 BM 的潜在诊断生物标志物。我们建立了一个可以提供 BM 个体诊断的模型。较高的 NfL 水平可能与 BM 患者的预后不良相关。
