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重型颅脑损伤患者血浆中lncRNA GAS5水平:与全身炎症及早期预后的相关性

Levels of lncRNA GAS5 in Plasma of Patients with Severe Traumatic Brain Injury: Correlation with Systemic Inflammation and Early Outcome.

作者信息

Lei Jin, Zhang Xiao, Tan Rui, Li Yu, Zhao Kai, Niu Hongquan

机构信息

Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Data Science Center, Clinical Development Division, CSPC Pharmaceutical Group Co., Ltd., Wuhan 430030, China.

出版信息

J Clin Med. 2022 Jun 9;11(12):3319. doi: 10.3390/jcm11123319.

Abstract

Scientific efforts continue to concentrate on elucidating the complex molecular mechanisms underlying traumatic brain injury (TBI), and recent reports suggest that epigenetic regulation including long non-coding RNA (lncRNA) is involved. The present study aimed to investigate the plasma concentration of a long non-coding RNA, named growth arrest-specific 5 (GAS5), in a group of 45 patients with severe TBI (sTBI), and to analyze the correlations of GAS5 with TBI onset, injury severity, systemic inflammation, and early outcome of the patients. It was found that plasma GAS5 levels were substantially increased in sTBI patients compared with the relative controls (p < 0.001). Further, significantly higher expression of plasma GAS5 was observed in patients with a Glasgow Coma Scale (GCS) score of less than five (p = 0.002) or unfavorable outcome at discharge (p < 0.001). Circulating GAS5 expression had a negative correlation with GCS score (r = −0.406, p = 0.006), and positive correlations with white blood cell count (r = 0.473, p = 0.001), neutrophil count (r = 0.502, p < 0.001), and neutrophil/lymphocyte ratio (NLR) (r = 0.398, p = 0.007). Univariate and multivariate logistic regression analyses revealed that GCS score (OR = 0.318, 95% CI 0.132−0.767, p = 0.011) and GAS5 (OR = 2.771, 95% CI 1.025−7.494, p = 0.045) were the two independent predictors for early outcome of patients. The receiver operating characteristic (ROC) curves showed good prognostic values of GCS score (AUC = 0.856, 95% CI: 0.719−0.943) and GAS5 expression (AUC = 0.798, 95% CI: 0.651−0.903). Importantly, the combined use of them can improve the prognostic ability of TBI with an AUC of 0.895 (95% CI: 0.767−0.966). Collectively, our study indicated that the levels of lncRNA GAS5 in circulation were elevated following severe TBI and correlated well with injury severity and inflammatory parameters. In addition, GAS5 as well as GCS scores may have the potential to predict the early outcome of TBI patients.

摘要

科学研究仍在持续聚焦于阐明创伤性脑损伤(TBI)背后复杂的分子机制,近期报告表明包括长链非编码RNA(lncRNA)在内的表观遗传调控与之相关。本研究旨在调查45例重度TBI(sTBI)患者血浆中一种名为生长停滞特异性5(GAS5)的长链非编码RNA的浓度,并分析GAS5与TBI发病、损伤严重程度、全身炎症及患者早期预后的相关性。研究发现,与相对对照组相比,sTBI患者血浆GAS5水平显著升高(p < 0.001)。此外,格拉斯哥昏迷量表(GCS)评分低于5分(p = 0.002)或出院时预后不良(p < 0.001)的患者血浆GAS5表达明显更高。循环GAS5表达与GCS评分呈负相关(r = -0.406,p = 0.006),与白细胞计数(r = 0.473,p = 0.001)、中性粒细胞计数(r = 0.502,p < 0.001)及中性粒细胞/淋巴细胞比值(NLR)(r = 0.398,p = 0.007)呈正相关。单因素和多因素逻辑回归分析显示,GCS评分(OR = 0.318,95%CI 0.132 - 0.767,p = 0.011)和GAS5(OR = 2.771,95%CI 1.025 - 7.494,p = 0.045)是患者早期预后的两个独立预测因素。受试者工作特征(ROC)曲线显示GCS评分(AUC = 0.856,95%CI:0.719 - 0.943)和GAS5表达(AUC = 0.798,95%CI:0.651 - 0.903)具有良好的预后价值。重要的是,两者联合使用可提高TBI的预后预测能力,AUC为0.895(95%CI:0.767 - 0.966)。总体而言,我们的研究表明,重度TBI后循环中lncRNA GAS5水平升高,且与损伤严重程度和炎症参数密切相关。此外,GAS5以及GCS评分可能具有预测TBI患者早期预后的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c080/9224922/81561cbefbe3/jcm-11-03319-g001.jpg

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