Refinement of saliva microRNA biomarkers for sports-related concussion

Hicks, Steven D.; Onks, Cayce; Kim, Raymond Y.; Zhen, Kevin; Loeffert, Jayson; Loeffert, Andrea C.; Olympia, Robert P.; Fedorchak, Gregory; DeVita, Samantha; Gagnon, Zofia; McLoughlin, Callan D.; Madeira, Miguel M.; Zuckerman, Scott L.; Lee, Timothy J.; Heller, Matthew; Monteith, Chuck; Campbell, Thomas R.; Neville, Christopher; Fengler, Elise; Dretsch, Michael N.

doi:10.1016/j.jshs.2021.08.003

Cited by 27 publications

(33 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of 1329 studies screened by abstract, 1277 were excluded for indicated reasons and 52 studies were selected for full-text review. A total of 9 studies [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ] were eligible for inclusion ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…The characteristics and key findings of the included studies are summarised in Table 1 , including the sex and age composition of populations, microRNAs extraction time, identified microRNAs and key findings. All the included studies were conducted in the UK [ 32 , 33 ] and USA [ 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Of the nine included studies [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ], four were case–control studies [ 33 , 34 , 37 , 38 ], three were cohort studies [ 32 , 39 , 40 ], one study used both case–control and cross-sectional study designs [ 36 ] and one study used case–cohort design [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

“…All the included studies were conducted in the UK [ 32 , 33 ] and USA [ 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Of the nine included studies [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ], four were case–control studies [ 33 , 34 , 37 , 38 ], three were cohort studies [ 32 , 39 , 40 ], one study used both case–control and cross-sectional study designs [ 36 ] and one study used case–cohort design [ 35 ]. Eight studies [ 32 , 33 , 34 , 36 , 37 , 38 , 39 , 40 ] involved subjects who had only mild TBI, with one study including a cohort of severe TBI [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Systematic Review of the Diagnostic and Clinical Utility of Salivary microRNAs in Traumatic Brain Injury (TBI)

Hiskens

Mengistu

et al. 2022

IJMS

View full text Add to dashboard Cite

Research in traumatic brain injury (TBI) is an urgent priority, as there are currently no TBI biomarkers to assess the severity of injury, to predict outcomes, and to monitor recovery. Small non-coding RNAs (sncRNAs) including microRNAs can be measured in saliva following TBI and have been investigated as potential diagnostic markers. The aim of this systematic review was to investigate the diagnostic or prognostic ability of microRNAs extracted from saliva in human subjects. PubMed, Embase, Scopus, PsycINFO and Web of Science were searched for studies that examined the association of saliva microRNAs in TBI. Original studies of any design involving diagnostic capacity of salivary microRNAs for TBI were selected for data extraction. Nine studies met inclusion criteria, with a heterogeneous population involving athletes and hospital patients, children and adults. The studies identified a total of 188 differentially expressed microRNAs, with 30 detected in multiple studies. MicroRNAs in multiple studies involved expression change bidirectionality. The study design and methods involved significant heterogeneity that precluded meta-analysis. Early data indicates salivary microRNAs may assist with TBI diagnosis. Further research with consistent methods and larger patient populations is required to evaluate the diagnostic and prognostic potential of saliva microRNAs.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Systematic Review of the Diagnostic and Clinical Utility of Salivary microRNAs in Traumatic Brain Injury (TBI)

Hiskens

Mengistu

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…1125 samples were collected with Oragene RNA stabilizer while 100 were collected without stabilizer. Three hundred and three participants provided repeat samples: there were 58 participants who provided samples in a fasting and non-fasting state [ 41 ], 93 participants who provided samples pre/post-exercise, and 152 participants who provided baseline samples two to six months apart [ 57 ].…”

Section: Methodsmentioning

confidence: 99%

Confounding Factors Impacting microRNA Expression in Human Saliva: Methodological and Biological Considerations

Sullivan

Montgomery

Scipioni

et al. 2022

Genes

View full text Add to dashboard Cite

There is growing interest in saliva microRNAs (miRNAs) as non-invasive biomarkers for human disease. Such an approach requires understanding how differences in experimental design affect miRNA expression. Variations in technical methodologies, coupled with inter-individual variability may reduce study reproducibility and generalizability. Another barrier facing salivary miRNA biomarker research is a lack of recognized “control miRNAs”. In one of the largest studies of human salivary miRNA to date (922 healthy individuals), we utilized 1225 saliva samples to quantify variability in miRNA expression resulting from aligner selection (Bowtie1 vs. Bowtie2), saliva collection method (expectorated vs. swabbed), RNA stabilizer (presence vs. absence), and individual biological factors (sex, age, body mass index, exercise, caloric intake). Differential expression analyses revealed that absence of RNA stabilizer introduced the greatest variability, followed by differences in methods of collection and aligner. Biological factors generally affected a smaller number of miRNAs. We also reported coefficients of variations for 643 miRNAs consistently present in saliva, highlighting several salivary miRNAs to serve as reference genes. Thus, the results of this analysis can be used by researchers to optimize parameters of salivary miRNA measurement, exclude miRNAs confounded by numerous biologic factors, and identify appropriate miRNA controls.

show abstract

“…Saliva miRNA levels change after head impacts, 9 , 10 differentiate individuals with concussion from non-concussed peers, 11 and display longitudinal patterns that mirror recovery trajectories. 12 These patterns may be useful in diagnosing concussion, 13-15 or predicting the duration of symptoms. 16 However, it is unclear whether miRNA patterns may be used to identify concussion phenotypes and guide individualized, biologically driven treatment plans.…”

Section: Introductionmentioning

confidence: 99%

Defining Biological Phenotypes of Mild Traumatic Brain Injury Using Saliva MicroRNA Profiles

Hicks

Leddy

Lichak

et al. 2022

Journal of Neurotrauma

Self Cite

View full text Add to dashboard Cite

Concussion is a heterogeneous injury that relies predominantly on subjective symptom reports for patient assessment and treatment. Developing an objective, biological test could aid phenotypic categorization of concussion patients, leading to advances in personalized treatment. This prospective multi-center study employed saliva micro-ribonucleic acid (miRNA) levels to stratify 251 individuals with concussion into biological subgroups. Using miRNA biological clusters, our objective was to assess for differences in medical/demographic characteristics, symptoms, and functional measures of balance and cognition. The miRNAs that best defined each cluster were used to identify physiological pathways that characterized each cluster. The 251 participants (mean age: 18 ± 7 years; 57% male) were optimally grouped into 10 clusters based on 22 miRNA levels. The clusters differed in age (χ 2 = 19.1, p = 0.024), days post-injury at the time of saliva collection (χ 2 = 22.6; p = 0.007), and number of prior concussions (χ 2 = 17.6, p = 0.040). The clusters also differed in symptom reports for fatigue (χ 2 = 17.7; p = 0.039), confusion (χ 2 = 22.3; p = 0.008), difficulty remembering (χ 2 = 22.0; p = 0.009), and trouble falling asleep (χ 2 = 17.2; p = 0.046), but not objective balance or cognitive performance ( p > 0.05). The miRNAs that defined concussion clusters regulate 16 physiological pathways, including adrenergic signaling, estrogen signaling, fatty acid metabolism, GABAergic signaling, synaptic vesicle cycling, and transforming growth factor (TGF)-β signaling. These results show that saliva miRNA levels may stratify individuals with concussion based on underlying biological perturbations that are relevant to both symptomology and pharmacological targets. If validated in a larger cohort, miRNA assessment could aid individualized, biology-driven concussion treatment.

show abstract

Refinement of saliva microRNA biomarkers for sports-related concussion

Cited by 27 publications

References 60 publications

Systematic Review of the Diagnostic and Clinical Utility of Salivary microRNAs in Traumatic Brain Injury (TBI)

Systematic Review of the Diagnostic and Clinical Utility of Salivary microRNAs in Traumatic Brain Injury (TBI)

Confounding Factors Impacting microRNA Expression in Human Saliva: Methodological and Biological Considerations

Defining Biological Phenotypes of Mild Traumatic Brain Injury Using Saliva MicroRNA Profiles

Contact Info

Product

Resources

About