与认知和平衡测试相比，使用唾液RNA诊断轻度创伤性脑损伤。
Diagnosing mild traumatic brain injury using saliva RNA compared to cognitive and balance testing.
作者信息
Hicks Steven D, Onks Cayce, Kim Raymond Y, Zhen Kevin J, Loeffert Jayson, Loeffert Andrea C, Olympia Robert P, Fedorchak Gregory, DeVita Samantha, Rangnekar Aakanksha, Leddy John, Haider Mohammad N, Gagnon Zofia, McLoughlin Callan D, Badia Matthew, Randall Jason, Madeira Miguel, Yengo-Kahn Aaron M, Wenzel Justin, Heller Matthew, Zwibel Hallie, Roberts Aaron, Johnson Samantha, Monteith Chuck, Dretsch Michael N, Campbell Thomas R, Mannix Rebekah, Neville Christopher, Middleton Frank
机构信息
Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania.
Department of Family Medicine, Penn State College of Medicine, Hershey, Pennsylvania.
出版信息
Clin Transl Med. 2020 Oct;10(6):e197. doi: 10.1002/ctm2.197.
BACKGROUND
Early, accurate diagnosis of mild traumatic brain injury (mTBI) can improve clinical outcomes for patients, but mTBI remains difficult to diagnose because of reliance on subjective symptom reports. An objective biomarker could increase diagnostic accuracy and improve clinical outcomes. The aim of this study was to assess the ability of salivary noncoding RNA (ncRNA) to serve as a diagnostic adjunct to current clinical tools. We hypothesized that saliva ncRNA levels would demonstrate comparable accuracy for identifying mTBI as measures of symptom burden, neurocognition, and balance.
METHODS
This case-control study involved 538 individuals. Participants included 251 individuals with mTBI, enrolled ≤14 days postinjury, from 11 clinical sites. Saliva samples (n = 679) were collected at five time points (≤3, 4-7, 8-14, 15-30, and 31-60 days post-mTBI). Levels of ncRNAs (microRNAs, small nucleolar RNAs, and piwi-interacting RNAs) were quantified within each sample using RNA sequencing. The first sample from each mTBI participant was compared to saliva samples from 287 controls. Samples were divided into testing (n = 430; mTBI = 201 and control = 239) and training sets (n = 108; mTBI = 50 and control = 58). The test set was used to identify ncRNA diagnostic candidates and create a diagnostic model. Model accuracy was assessed in the naïve test set.
RESULTS
A model utilizing seven ncRNA ratios, along with participant age and chronic headache status, differentiated mTBI and control participants with a cross-validated area under the curve (AUC) of .857 in the training set (95% CI, .816-.903) and .823 in the naïve test set. In a subset of participants (n = 321; mTBI = 176 and control = 145) assessed for symptom burden (Post-Concussion Symptom Scale), as well as neurocognition and balance (ClearEdge System), these clinical measures yielded cross-validated AUC of .835 (95% CI, .782-.880) and .853 (95% CI, .803-.899), respectively. A model employing symptom burden and four neurocognitive measures identified mTBI participants with similar AUC (.888; CI, .845-.925) as symptom burden and four ncRNAs (.932; 95% CI, .890-.965).
CONCLUSION
Salivary ncRNA levels represent a noninvasive, biologic measure that can aid objective, accurate diagnosis of mTBI.
背景
早期、准确诊断轻度创伤性脑损伤（mTBI）可改善患者的临床结局，但由于依赖主观症状报告，mTBI的诊断仍然困难。一种客观的生物标志物可以提高诊断准确性并改善临床结局。本研究的目的是评估唾液非编码RNA（ncRNA）作为当前临床工具辅助诊断的能力。我们假设唾液ncRNA水平在识别mTBI方面将表现出与症状负担、神经认知和平衡测量相当的准确性。
方法
这项病例对照研究涉及538名个体。参与者包括251名mTBI患者，在受伤后≤14天入组，来自11个临床地点。在五个时间点（mTBI后≤3天、4 - 7天、8 - 14天、15 - 30天和31 - 60天）收集唾液样本（n = 679）。使用RNA测序对每个样本中的ncRNA（微小RNA、小核仁RNA和piwi相互作用RNA）水平进行定量。将每个mTBI参与者的第一个样本与287名对照的唾液样本进行比较。样本分为测试集（n = 430；mTBI = 201，对照 = 239）和训练集（n = 108；mTBI = 50，对照 = 58）。测试集用于识别ncRNA诊断候选物并创建诊断模型。在原始测试集中评估模型准确性。
结果
一个利用七个ncRNA比率以及参与者年龄和慢性头痛状态的模型，在训练集中区分mTBI和对照参与者的交叉验证曲线下面积（AUC）为0.857（95%CI，0.816 - 0.903），在原始测试集中为0.823。在一组评估症状负担（脑震荡后症状量表）以及神经认知和平衡（ClearEdge系统）的参与者（n = 321；mTBI = 176，对照 = 145）中，这些临床测量的交叉验证AUC分别为0.835（95%CI，0.782 - 0.880）和0.853（95%CI，0.803 - 0.899）。一个采用症状负担和四种神经认知测量的模型识别mTBI参与者的AUC（0.888；CI, 0.845 - 0.925）与症状负担和四种ncRNA（0.932；95%CI，0.890 - 0.965）相似。
结论
唾液ncRNA水平代表一种非侵入性的生物学测量方法，可有助于客观、准确地诊断mTBI。
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