The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
Department of Neurosurgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, People's Republic of China.
Clin Chim Acta. 2023 May 1;545:117370. doi: 10.1016/j.cca.2023.117370.
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is released under endoplasmic reticulum stress, thereby exerting neuroprotective effects. We determined whether serum MANF may be a prognostic biomarker of human severe traumatic brain injury (sTBI).
Serum MANF concentrations of 137 sTBI patients and 137 controls were quantified in this prospective cohort study. Patients with extended Glasgow outcome scale (GOSE) scores of 1-4 at post-traumatic 6 months were considered to have poor prognosis. Relationships between serum MANF concentrations and severity plus prognosis were investigated using multivariate analyses. Area under receiver operating characteristic curve (AUC) was calculated for reflecting prognostic efficiency.
As compared to controls, there was a significant increase of serum MANF concentrations after sTBI (median, 18.5 ng/ml versus 3.0 ng/ml; P < 0.001), which was independently correlated with Glasgow coma scale (GCS) scores [β, -3.000; 95% confidence interval (CI), -4.525--1.476; VIF, 2.216; P = 0.001], Rotterdam computed tomography (CT) scores (β, 4.020; 95% CI, 1.446-6.593; VIF, 2.234; P = 0.002) and GOSE scores (β, -0.056; 95% CI, -0.089--0.023; VIF, 1.743; P = 0.011). Serum MANF concentrations substantially distinguished risk of poor prognosis with AUC of 0.795 (95% CI, 0.718-0.859) and its concentrations > 23.9 ng/ml was predictive of poor prognosis with 67.7% sensitivity and 81.9% specificity. Serum MANF concentrations combined with GCS scores and Rotterdam CT scores displayed markedly higher prognostic predictive ability than each of them (all P < 0.05). Using restricted cubic spline, there was a linear correlation between serum MANF concentrations and poor prognosis (P = 0.256). Serum MANF concentrations > 23.9 ng/ml was independently associated with poor prognosis (odds ratio, 2.911; 95% CI, 1.057-8.020; P = 0.039). A nomogram was built, where serum MANF concentrations > 23.9 ng/ml, GCS scores and Rotterdam CT scores were integrated. Hosmer and Lemeshow test, calibration curve and decision curve analysis demonstrated such a prediction model was comparatively stable and was of relatively high clinical benefit.
Substantially increased serum MANF concentrations after sTBI are highly correlated with traumatic severity and are independently predictive of long-term poor prognosis, suggesting that serum MANF may represent a useful prognostic biochemical marker of human sTBI.
中脑星形胶质细胞衍生的神经营养因子（MANF）在内质网应激下释放，从而发挥神经保护作用。我们确定血清 MANF 是否可能是人类严重创伤性脑损伤（sTBI）的预后生物标志物。
在这项前瞻性队列研究中，对 137 名 sTBI 患者和 137 名对照者的血清 MANF 浓度进行了定量分析。在创伤后 6 个月，格拉斯哥结局量表（GOSE）评分扩展为 1-4 的患者被认为预后不良。使用多元分析研究了血清 MANF 浓度与严重程度和预后之间的关系。计算了接收器操作特征曲线（ROC）的曲线下面积（AUC），以反映预后效率。
与对照组相比，sTBI 后血清 MANF 浓度显著升高（中位数，18.5ng/ml 与 3.0ng/ml；P<0.001），这与格拉斯哥昏迷评分（GCS）评分独立相关[β，-3.000；95%置信区间（CI），-4.525--1.476；VIF，2.216；P=0.001]、鹿特丹 CT 评分（β，4.020；95%CI，1.446-6.593；VIF，2.234；P=0.002）和 GOSE 评分（β，-0.056；95%CI，-0.089--0.023；VIF，1.743；P=0.011）。血清 MANF 浓度具有较高的区分预后不良风险的能力，AUC 为 0.795（95%CI，0.718-0.859），其浓度>23.9ng/ml 可预测预后不良，灵敏度为 67.7%，特异性为 81.9%。血清 MANF 浓度与 GCS 评分和鹿特丹 CT 评分相结合，显示出明显更高的预后预测能力（均 P<0.05）。使用限制性立方样条，血清 MANF 浓度与预后不良之间存在线性关系（P=0.256）。血清 MANF 浓度>23.9ng/ml 与预后不良独立相关（优势比，2.911；95%CI，1.057-8.020；P=0.039）。建立了一个列线图，其中整合了血清 MANF 浓度>23.9ng/ml、GCS 评分和鹿特丹 CT 评分。Hosmer 和 Lemeshow 检验、校准曲线和决策曲线分析表明，该预测模型比较稳定，具有较高的临床获益。
sTBI 后血清 MANF 浓度显著升高，与创伤严重程度高度相关，且独立预测长期预后不良，提示血清 MANF 可能是人类 sTBI 有用的预后生化标志物。
