Tag: Biomarker

Posted on

Exploring the Diagnostic Test Accuracy of MicroRNAs as Potential Biomarkers for Glioblastoma

Neurosurgery 98:1221–1230, 2026

This systematic review and meta-analysis evaluates microRNA (miRNA)–based liquid biopsies for diagnosing glioblastoma (GBM), synthesizing data from 15 studies and 28 biomarker evaluations across 868 samples. Key diagnostic metrics—pooled sensitivity 0.84 and specificity 0.89—indicate strong potential, with miR-21 showing the highest accuracy among single-miRNA assays.

The report details search strategy, inclusion criteria, statistical methods, subgroup analyses (miRNA type, biofluid source, control type), and study quality assessment. Limitations include methodological heterogeneity, high risk of bias in patient selection, inconsistent reporting (CSF source, IDH status), and small cohort sizes, underscoring need for standardized clinical validation.

Aim Evaluate the diagnostic accuracy of microRNA (miRNA) liquid biopsies (blood/serum/plasma/CSF) for diagnosing glioblastoma (GBM) via systematic review and meta-analysis.

Methods PRISMA-guided searches of Ovid Medline and Embase (updated through Oct 16, 2024); included studies had histologic GBM confirmation and extractable 2×2 diagnostic data; pooled estimates generated using a random-effects bivariate model.

Evidence base 15 included articles (published 2011–2022) provided 28 miRNA evaluations, totaling 868 samples from 551 GBM patients and 811 samples from 578 controls.

Overall accuracy Pooled sensitivity 0.84 and specificity 0.89, with heterogeneity of 66% (sensitivity) and 39% (specificity); pooled AUC 0.89.

Likelihood ratios Pooled PLR 7.26, NLR 0.19, and DOR 40.17, indicating strong overall discriminatory performance.

Key biomarker miR-21 showed the highest pooled performance among assessed groupings (sensitivity 0.90, specificity 0.95).

Subgroups Single miRNAs had higher specificity than multi-miRNA panels, while diagnostic capability did not differ clearly by biofluid source (CSF vs blood) in this dataset.

Limitations All included studies had high risk of bias in patient selection, and many had bias in index test interpretation/flow-timing; limited CSF comparisons and inconsistent qPCR thresholds/normalization contributed to heterogeneity and constrain clinical translation without standardization and validation.

Posted on

Wall enhancement as a biomarker of intracranial aneurysm instability: a histo‑radiological study

Acta Neurochirurgica (2023) 165:2783–2791

The aim of this is to explore the histological basis of vessel wall enhancement (WE) on magnetic resonance imaging (MRI), which is a strong radiological biomarker of aneurysmal prone to rupture compared to other classical risk predictors (e.g., PHASES score, size, morphology).

Methods A prospective observational study was performed including all consecutive patients presenting with a saccular intracranial aneurysm at Vall d’Hebron University Hospital between October 2017 and May 2019. The patients underwent high-resolution 3 T MRI, and their aneurysms were classified into asymptomatic, symptomatic, and ruptured. A histological and immunohistochemical study was performed in a subgroup of patients (n = 20, of which 15 presented with WE). Multiple regression analyses were performed to identify predictors of rupture and aneurysm symptoms.

Results A total of 132 patients were enrolled in the study. WE was present in 36.5% of aneurysms: 22.9% asymptomatic, 76.9% symptomatic, and 100% ruptured. Immunohistochemical markers associated with WE were CD3 T cell receptor (p = 0.05) and CD45 leukocyte common antigen (p = 0.05). Moreover, WE is an independent predictor of symptomatic and ruptured aneurysms (p < 0.001).

Conclusions Aneurysms with WE present multiple histopathological changes that may contribute to wall disruption and represent the pathophysiological basis of radiological WE. Moreover, WE is an independent diagnostic predictor of aneurysm symptoms and rupture.

Posted on

The WHO 2021 Classification of Central Nervous System tumours: a practical update on what neurosurgeons need to know—a minireview

Acta Neurochirurgica (2022) 164:2453–2464

The World Health Organization (WHO) Classification of Tumours, also known as WHO Blue Books, represents an international standardised tool in the diagnostic work-up of tumours. This classification system is under continuous revision, and progress in the molecular classification of tumours in the central nervous system (CNS) enforced an update of the WHO 2016 classification, and the fifth edition, WHO CNS5, was published in 2021. The aim of this minireview is to highlight important changes in this new edition relevant for the practicing neurosurgeon.

Methods The sixth volume of the fifth edition of the WHO Blue Books of CNS tumours and related papers formed the basis for this minireview.

Results Major changes encompass standardisation of tumour grading and nomenclature as well as increased incorporation of molecular markers in the classification of CNS tumours.

Conclusion Advances in molecular genetics have resulted in more accurate diagnosis and prognosis of CNS tumours, and this minireview summarises important changes implemented in the last edition of WHO classification of CNS tumours important for the practicing neurosurgeon.

Posted on

Cerebrospinal fluid and venous biomarkers of shunt‐responsive idiopathic normal pressure hydrocephalus: a systematic review and meta‐analysis

Acta Neurochirurgica (2022) 164:1719–1746

Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH.

Objective To conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt- responsive iNPH most accurately.

Methods Original studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses.

Results The study included 13 studies; seven addressed lumbar CSF levels of amyloid-β 1–42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-β 1–42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (− 0.55 SMD, p = 0.04) and Total-Tau (− 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-β 1–42 (− 0.26 SMD, p = 0.55) or the other included biomarkers.

Conclusion This meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-β 1–42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.

Posted on

Circulating serum oncologic miRNA in pediatric juvenile pilocytic astrocytoma patients predicts mural nodule volume

Acta Neurochirurgica (2018) 160:1571–1581

Juvenile pilocytic astrocytomas represent the largest group of pediatric brain tumors. The ideal management for these tumors is early, total surgical resection. To detect and track treatment response, a screening tool is needed to identify patients for surgical evaluation and assess the quality of treatment. The identification of aberrant miRNA profiles in the sera of juvenile pilocytic astrocytoma patients could provide such a screening tool.

Methods The authors reviewed the serum profiles of 84 oncologically relevant miRNAs in pediatric juvenile pilocytic astrocytoma patients via qPCR screening.

Results miR-21, miR-15b, miR-23a, and miR-146b were significantly elevated in the sera of JPA patients as compared to nononcologic controls, oncologic controls, and post-JPA resection samples (p < 0.001, 0.022, 0.034, 0.044). miR-21 had the highest AUC on ROC analysis (AUC > 0.99, sensitivity 75%, specificity 100%). All four miRNAs also correlated well with tumor mural nodule size, though they only poorly correlated with total tumor size, including cystic components (Spearman’s R2: miR-21 91.7 vs 6.9%, miR-15b 86.3 vs 23.1%, miR-23a 85.8 vs 23.0%, miR-146b 59.8 vs 11.9%).

Conclusion In this small pilot study, pediatric juvenile pilocytic astrocytoma patients had significant elevations in serum miR-21, miR-15b, miR-23a, and miR-146b levels that do not appear to be driven by hydrocephalus or local distortion of the intracranial contents. These alterations correlate with solid tumor component volume and reverse with complete tumor resection, suggesting that this serum miRNA profile may delineate biomarkers for screening and tracking juvenile pilocytic astrocytoma patients. Additional studies, with a larger cohort, are needed to verify these results.

Posted on

Diffusion Tensor Imaging: A Possible Biomarker in Severe Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage?

diffusion-tensor-imaging-a-possible-biomarker-in-severe-traumatic-brain-injury-and-aneurysmal-subarachnoid-hemorrhage

Neurosurgery 79:786–793, 2016

A great need exists in traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (aSAH) for objective biomarkers to better characterize the disease process and to serve as early endpoints in clinical studies. Diffusion tensor imaging (DTI) has shown promise in TBI, but much less is known about aSAH.

OBJECTIVE: To explore the use of whole-brain DTI tractography in TBI and aSAH as a biomarker and early endpoint.

METHODS: Of a cohort of 43 patients with severe TBI (n = 20) or aSAH (n = 23) enrolled in a prospective, observational, multimodality monitoring study, DTI data were acquired at approximately day 12 (median, 12 days; interquartile range, 12-14 days) after injury in 22 patients (TBI, n = 12; aSAH, n = 10). Whole-brain DTI tractography was performed, and the following parameters quantified: average fractional anisotropy, mean diffusivity, tract length, and the total number of reconstructed fiber tracts. These were compared between TBI and aSAH patients and correlated with mortality and functional outcome assessed at 6 months by the Glasgow Outcome Scale Extended.

RESULTS: Significant differences were found for fractional anisotropy values (P = .01), total number of tracts (P = .03), and average tract length (P = .002) between survivors and nonsurvivors. A sensitivity analysis showed consistency of results between the TBI and aSAH patients for the various DTI measures.

CONCLUSION: DTI parameters, assessed at approximately day 12 after injury, correlated with mortality at 6 months in patients with severe TBI or aSAH. Similar patterns were found for both TBI and aSAH patients. This supports a potential role of DTI as early endpoint for clinical studies and a predictor of late mortality.

Posted on

MicroRNAs as Biomarkers in Pituitary Tumors

MicroRNAs_as_Biomarkers_in_Pituitary_Tumors

Neurosurgery 75:181–189, 2014

The use of extracellular microRNAs (miRNAs) as circulating biomarkers is currently leading to relevant advances in the diagnosis and assessment of prognosis of several diseases.

Specific miRNAs have also been shown to play a role in the pathophysiology of many neoplastic and non-neoplastic diseases. A number of studies have demonstrated that miRNAs show differential expression in various tumors, such as in the prostate, ovary, lung, breast, brain, and pituitary.

Recent findings have built connections between miRNAs that are deregulated within the tumor and their presence in peripheral blood. MiRNAs have been shown to be stable in the blood where they are present in either free and/or uncomplexed form, as well as packed in microvesicles, exosomes, and apoptotic bodies, or bound to different proteins.

Because the pituitary is a highly vascularized organ that releases hormones into the circulation, miRNAs would be useful biomarkers for the diagnosis of pituitary tumors, as well as for predicting or detecting recurrence after surgery.

Here we review the biological significance of miRNAs in pituitary tumors and the potential value of circulating miRNAs as biomarkers.

Posted on

Proteomic analysis of cerebrospinal fluid: toward the identification of biomarkers for gliomas

Proteomics

Neurosurg Rev (2014) 37:367–380

Gliomas are the most common primary brain tumors in adults and, despite advances in the understandings of glioma pathogenesis in the genetic era, they are still ineradicable, justifying the need to develop more reliable diagnostic and prognostic biomarkers for this malignancy. Because changes in cerebrospinal fluid (CSF) are suggested to be capable of sensitively reflecting pathological processes, e.g., neoplastic conditions, in the central nervous system, CSF has been deemed a valuable source for potential biomarkers screening in this era of proteomics.

This systematic review focused on the proteomic analysis of glioma CSF that has been published to date and identified a total of 19 differentially expressed proteins. Further functional and protein-protein interaction assessments were performed by using Protein Analysis Through Evolutionary Relationships (PANTHER) website and Ingenuity Pathway Analysis (IPA) software, which revealed several important protein networks (e.g., IL- 6/STAT-3) and four novel focus proteins (IL-6, galanin (GAL), HSPA5, andWNT4) that might be involved in glioma pathogenesis.

The concentrations of these focus proteins were subsequently determined by enzyme-linked immunosorbent assay (ELISA) in an independent set of CSF and tumor cyst fluid (CF) samples. Specifically, glioblastoma (GBM) CF had significantly lower GAL, HSPA5, andWNT4 levels than CSF from different grades of glioma. In contrast, IL-6 level was significantly higher in GBM CF when compared with CSF and, among different CSF groups, was highest in GBM CSF.

Therefore, these candidate protein biomarkers, identified from both the literatures and in silico analysis, may have potentials in clinical diagnosis, prognosis evaluation, treatment response monitoring, and novel therapeutic targets identification for patients with glioma.

Proudly powered by WordPress