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pmid:40626048

Identification of potential miRNA biomarkers for neurobrucellosis diagnosis.

Meiling Liu · Liping Feng · Shujun Shi · Yuzhou Guo · Menghan Lv · Zhengyu Li · Xintian Wang · Hao Yang · Zhelin Zhang

Frontiers in physiology · 2025 doi:10.3389/fphys.2025.1463597

Paper

complete

Experiment

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Data

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Analysis

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Execution

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title
Identification of potential miRNA biomarkers for neurobrucellosis diagnosis.
doi
10.3389/fphys.2025.1463597
pmid
40626048
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[0]
Meiling Liu
[1]
Liping Feng
[2]
Shujun Shi
[3]
Yuzhou Guo
[4]
Menghan Lv
[5]
Zhengyu Li
[6]
Xintian Wang
[7]
Hao Yang
[8]
Zhelin Zhang
journal
Frontiers in physiology
year
2025
abstract
Background: Neurobrucellosis (NB) is a rare complication of brucellosis that presentis with a variety of clinical symptoms, complicating its diagnosis. This study aimed to analyze the microRNA (miRNA) profile of cerebrospinal fluid (CSF) in NB patients to identify potential biomarkers for NB diagnosis. Methods: Small RNA sequencing was utilized to identify differential expressed miRNAs (DEmiRNAs) in CSF samples from both control and NB patients (in-house cohort). The GSE107554 dataset (validation cohort) from the GEO database was used to validate the expression levels of these DEmiRNAs. Subsequently, LASSO regression analysis was conducted to construct a diagnostic risk score model based on common miRNAs identified in both the in-house and validation cohorts. Results: The study identified 51 DEmiRNAs between the control and NB groups, based on the data from the in-house cohort. Among these, four common miRNAs (miR-342-3p, miR-576-5p, miR-15b-5p and miR-499a-5p) were significantly elevated in the infection group compared to controls in both the in-house and validation cohorts. Subsequently, a novel NB diagnostic signature comprising two miRNAs (miR-576-5p and miR-499a-5p) was developed using the LASSO regression analysis. Receiver operating characteristic (ROC) analysis demonstrated the good diagnostic potential of this miRNA signature in both cohorts. RT-qPCR analysis indicated elevated levels of miR-576-5p and miR-499a-5p in CSF samples of NB patients compared to controls. Additionally, RT-qPCR results revealed decreased levels of VAV3 (vav guanine nucleotide exchange factor 3, a target of miR-499a-5p) and IGF1 (insulin like growth factor 1, a target of miR-576-5p) in the CSF samples of NB patients. Conclusion: Collectively, miR-576-5p and miR-499a-5p may serve as potential biomarkers for the diagnosis of NB.
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LASSO Cox regression analysis with was conducted using the “glmnet” package in R language to further identify miRNAs associated with NB (Friedman et al., 2010).
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A two-miRNA diagnostic signature comprising miR-576-5p and miR-499a-5p showed strong diagnostic performance for neurobrucellosis, with ROC AUC values of 1.000 in the in-house cohort and 0.875 in the validation cohort.
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As shown in Figures 4B, C, the AUC value of the ROC curve was 1.000 in the in-house cohort, and was 0.875 in the validation cohort, indicating that the risk score may have a good diagnostic performance.
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A two-miRNA diagnostic signature comprising miR-576-5p and miR-499a-5p showed strong diagnostic performance for neurobrucellosis, with ROC AUC values of 1.000 in the in-house cohort and 0.875 in the validation cohort.
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biomarkers for NB diagnosis. Methods: Small RNA sequencing was utilized to identify differential expres
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ial of this miRNA signature in both cohorts. RT-qPCR analysis indicated elevated levels of miR-57
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patients compared to controls. Additionally, RT-qPCR results revealed decreased levels of VAV3 (v
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of this miRNA signature in both cohorts. RT-qPCR analysis indicated elevated levels of miR-57
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ients compared to controls. Additionally, RT-qPCR results revealed decreased levels of VAV3 (v
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Complete file
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This study aimed to analyze the microRNA (miRNA) profile of cerebrospinal fluid (CSF) in NB patients to identify potential biomarkers for NB diagnosis.\nMethods: Small RNA sequencing was utilized to identify differential expressed miRNAs (DEmiRNAs) in CSF samples from both control and NB patients (in-house cohort). The GSE107554 dataset (validation cohort) from the GEO database was used to validate the expression levels of these DEmiRNAs. Subsequently, LASSO regression analysis was conducted to construct a diagnostic risk score model based on common miRNAs identified in both the in-house and validation cohorts.\nResults: The study identified 51 DEmiRNAs between the control and NB groups, based on the data from the in-house cohort. Among these, four common miRNAs (miR-342-3p, miR-576-5p, miR-15b-5p and miR-499a-5p) were significantly elevated in the infection group compared to controls in both the in-house and validation cohorts. Subsequently, a novel NB diagnostic signature comprising two miRNAs (miR-576-5p and miR-499a-5p) was developed using the LASSO regression analysis. Receiver operating characteristic (ROC) analysis demonstrated the good diagnostic potential of this miRNA signature in both cohorts. RT-qPCR analysis indicated elevated levels of miR-576-5p and miR-499a-5p in CSF samples of NB patients compared to controls. Additionally, RT-qPCR results revealed decreased levels of VAV3 (vav guanine nucleotide exchange factor 3, a target of miR-499a-5p) and IGF1 (insulin like growth factor 1, a target of miR-576-5p) in the CSF samples of NB patients.\nConclusion: Collectively, miR-576-5p and miR-499a-5p may serve as potential biomarkers for the diagnosis of NB.", "claims": [{"id": "claim-method", "statement": "LASSO Cox regression analysis with was conducted using the “glmnet” package in R language to further identify miRNAs associated with NB (Friedman et al., 2010).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40626048", "locator": "sections[8] \"2.6 LASSO regression analysis\" paragraph 2", "quote": "LASSO Cox regression analysis with was conducted using the “glmnet” package in R language to further identify miRNAs associated with NB (Friedman et al., 2010)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data supporting the conclusions of this study are openly available at https://www.ncbi.nlm.nih.gov/search/all/?term=PRJNA1272809, reference number PRJNA1272809.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40626048", "locator": "sections[22] \"Data availability statement\" paragraph 2", "quote": "Data supporting the conclusions of this study are openly available at https://www.ncbi.nlm.nih.gov/search/all/?term=PRJNA1272809, reference number PRJNA1272809."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A two-miRNA diagnostic signature comprising miR-576-5p and miR-499a-5p showed strong diagnostic performance for neurobrucellosis, with ROC AUC values of 1.000 in the in-house cohort and 0.875 in the validation cohort.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40626048", "locator": "sections[16] \"3.3 Construction a diagnostic risk score model\" paragraph 2", "quote": "As shown in Figures 4B, C, the AUC value of the ROC curve was 1.000 in the in-house cohort, and was 0.875 in the validation cohort, indicating that the risk score may have a good diagnostic performance."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A two-miRNA diagnostic signature comprising miR-576-5p and miR-499a-5p showed strong diagnostic performance for neurobrucellosis, with ROC AUC values of 1.000 in the in-house cohort and 0.875 in the validation cohort.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40626048"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE107554"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE107554"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40626048", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphys.2025.1463597", "sha256": 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