Blood RNA biomarkers for spinal cord injury
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE151371 | GEO | 2021/01/22
REPOSITORIES: GEO
Similar Datasets
Project description:Background: Long noncoding RNAs (lncRNAs) have been confirmed to be associated with ischemic stroke (IS); however, their involvement still needs to be extensively explored. Therefore, we aimed to study the expression profile of lncRNAs and the potential roles and mechanisms of lncRNAs in the pathogenesis of acute ischemic stroke (AIS) in the Southern Chinese Han population. Methods: lncRNA and mRNA expression profiles in AIS were analyzed using high-throughput RNA sequencing (RNA-Seq) and validated using quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and network analyses were performed to predict the functions and interactions of the aberrantly expressed genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of lncRNAs in AIS. Results: RNA-Seq analysis showed that 428 lncRNAs and 957 mRNAs were significantly upregulated, while 791 lncRNAs and 4263 mRNAs were downregulated in patients with AIS when compared with healthy controls. GO enrichment and KEGG pathway analyses of differentially expressed genes showed that the apoptosis, inflammatory, oxidative and calcium signaling pathways were potentially implicated in AIS pathology. The PCR results showed that the selected lncRNA-C14orf64 and lncRNA-AC136007.2 were significantly downregulated in AIS. ROC curve analysis showed that the area under the ROC curve (AUC) values of lncRNA-C14orf64 and lncRNA-AC136007.2 between AIS and healthy controls were 0.74 and 0.94, respectively. Conclusion: This study provides evidence of altered expression of lncRNAs and their potential functions in AIS. Our findings may facilitate pathological mechanistic studies of lncRNAs in AIS and provide potential diagnostic biomarkers and therapeutic targets for AIS.
2019-11-13 | GSE140275 | GEO
Project description:The primary aim of this work was to investigage the proteomic differences across spinal cord injury (SCI) patients who experience significant functional recovery relative to those who do not, to both better understand the pathophysiology and to identify potentially useful biomarkers of recovery. Blood samples were taken, following informed consent, from ASIA impairment scale (AIS) grade C "Improvers" (AIS grade improvement) (n=10 & n=9) and "Non-Improvers" (No AIS change) (n=7 & n=6), and AIS grade A (n=11 & n= 9) and D (n=11 & n=10) at <2 weeks ("Acute") and approx. 3 months ("Sub-acute") post-injury for a total of 73 samples. The samples were treated with ProteoMiner™ beads. Data dependent label-free LC-MSMS was used to characterise the proteome of the samples.
2022-07-14 | PXD035072 | Pride
Project description:Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of CSF and serum samples from 111 acute SCI patients and, in parallel, a large animal (porcine) model of SCI. We develop and validate protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at six months with an AUC of 0.91. Through comparative proteomic analyses, we dissect conserved and divergent aspects of the SCI response, and establish the CSF abundance of glial fibrillary acidic protein (GFAP) as a biochemical outcome measure in both human and pig. Our work defines new resources to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.
2020-06-09 | MSV000085567 | MassIVE
Project description:Biomarkers to more accurately determine severity and prognosis following spinal cord injury (SCI) are needed to ensure that patients are assigned to the most suitable treatment and rehabilitation regimes. This study aimed to characterise the blood proteome following SCI in clinical rat injury models to identify novel candidate biomarkers and altered biological pathways.
2022-05-19 | PXD021137 | Pride
Project description:Spinal cord injury (SCI) is a devastating neurological condition for which there are currently no effective treatment options to restore function. A major obstacle to the development of new therapies is our fragmentary understanding of the coordinated pathophysiological processeses triggered by damage to the human spinal cord. An additional challenge to translation of preclinical therapies is the reliance of clinical trials on standardized neurological assessments to enrol and stratify patients, rather than objective injury biomarkers. Here, we describe a systems biology approach to integrate decades of small-scale experiments with unbiased, genome-wide gene expression from the human spinal cord, revealing a gene regulatory network signature of the pathophysiological response to SCI. Our integrative analyses converge on an evolutionarily conserved gene subnetwork enriched for genes associated with the response to SCI by small-scale experiments, and whose expression is upregulated in a severity-dependent manner following injury and downregulated in functional recovery. We validate the severity-dependent upregulation of this subnetwork in prospective transcriptomic and proteomic studies. Our analysis provides a systems-level view of the coordinated molecular processes activated in response to SCI. Further, our results nominate quantitative biomarkers of injury severity and functional recovery, with the potential to facilitate development and translation of novel therapies.
2018-09-25 | PXD010192 | Pride
Project description:Traumatic spinal cord injury (SCI) may induce irreversible damage leading to severe incapacity. Molecular mechanisms underlying SCI are not fully understood, preventing the development of novel therapeutic resources. Tamoxifen has demonstrated to be a promising therapy. Our aim was to elucidate the molecular mechanisms involved in the beneficial effect of TMX administered after SCI. We use a rat model of SCI, Tamoxifen was administred intraperitoneal 30 min after injury. Four groups were organized, 1) Non-injured without TMX (Sham/TMX-), 2) Non-injured with TMX (Sham/TMX+), 3) Injured without TMX (SCI/TMX-), and 4) Injured with TMX (SCI/TMX+). From the comparison between Sham/TMX- and SCI/TMX-, 708 genes showed differential expression. Among the relevant genes Anxa1 was upregulated, this gene’s product is a promising marker of injury severity. Enriched pathways were the spinal cord injury pathway and pathways related to inflammatory response. When comparing SCI/TMX- versus SCI/TMX+, only 30 genes showed differential expression. Our results reinforce the key role of inflammatory response in SCI and Tamoxifen seem to be able to regulate this response by suppressing changes in gene expression. Our data also support the potential of previously described severity markers.
2023-09-14 | GSE229618 | GEO
Project description:Spinal cord injury (SCI) is a devastating neurological condition for which there are currently no effective treatment options to restore function. A major obstacle to the development of new therapies is our fragmentary understanding of the coordinated pathophysiological processeses triggered by damage to the human spinal cord. An additional challenge to translation of preclinical therapies is the reliance of clinical trials on standardized neurological assessments to enrol and stratify patients, rather than objective injury biomarkers. Here, we describe a systems biology approach to integrate decades of small-scale experiments with unbiased, genome-wide gene expression from the human spinal cord, revealing a gene regulatory network signature of the pathophysiological response to SCI. Our integrative analyses converge on an evolutionarily conserved gene subnetwork enriched for genes associated with the response to SCI by small-scale experiments, and whose expression is upregulated in a severity-dependent manner following injury and downregulated in functional recovery. We validate the severity-dependent upregulation of this subnetwork in prospective transcriptomic and proteomic studies. Our analysis provides a systems-level view of the coordinated molecular processes activated in response to SCI. Further, our results nominate quantitative biomarkers of injury severity and functional recovery, with the potential to facilitate development and translation of novel therapies.
2018-10-02 | GSE115067 | GEO
Project description:Chronic, often intractable pain is caused by neuropathic conditions such as peripheral nerve injury (PNI) and spinal cord injury (SCI). These conditions are associated with alterations in gene and protein expression correlated with functional changes in somatosensory neurons having cell bodies in dorsal root ganglia (DRGs). Most studies of DRG transcriptional alterations have utilized PNI models where axotomy-induced changes important for regeneration may overshadow changes that drive neuropathic pain. Both PNI and SCI produce DRG neuron hyperexcitability linked to pain, but contusive SCI produces little peripheral axotomy or peripheral nerve inflammation. Thus, comparison of transcriptional signatures of DRGs across PNI and SCI models may highlight pain-associated transcriptional alterations that don’t depend on peripheral axotomy and associated effects such as peripheral Wallerian degeneration. Data from our rat thoracic SCI experiments were combined with meta-analysis of whole-DRG RNA-seq datasets from prominent rat PNI models. Striking differences were found between transcriptional responses to PNI and SCI, especially in regeneration-associated genes and long noncoding RNAs. Many transcriptomic changes after SCI were also found after corresponding sham surgery, indicating they were caused by injury to surrounding tissue rather than to the spinal cord itself. Another unexpected finding was of few transcriptomic similarities between any rat neuropathic pain model and the only reported transcriptional analysis of human DRGs linked to neuropathic pain. These findings show that DRGs exhibit complex transcriptional responses to central and peripheral neural and tissue injury. Although few genes in DRG cells show similar changes in gene expression across all these painful conditions, the few widely shared transcriptional alterations promise novel insights into fundamental mechanisms within DRGs that can drive neuropathic pain.
2022-10-20 | GSE202111 | GEO
Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples Retrospective, mutli-site sutdy using retrospective physician adjudication as a comparator
2015-10-24 | E-GEOD-74224 | biostudies-arrayexpress
Project description:Individuals with SCI are severely affected by immune system changes, resulting in a SCI-induced immune deficiency syndrome (SCI-IDS). While recent data support that acute SCI-IDS symptoms differ from those present in the chronic phase, only limited data in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR<0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI were observed. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, indicating a persistent ‘neurogenic’ imprint. Overall, 2876 DE genes emerge when comparing profiles of motor complete to motor incomplete SCI (ANOVA, FDR<0.05), including genes related to neutrophils, inflammation, and infection. In summary, we identify dynamic SCI-IDS determinants in humans, including molecular and cellular profiles, which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.
2023-05-26 | GSE226238 | GEO