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Cerebrospinal Fluid MicroRNA Profiling Using Quantitative Real Time PCR
Published on: January 22, 2014
Altered exosomal miRNA profiles in patients with paraneoplastic cerebellar degeneration
Eirik Tveit Solheim1,2, Liv Cecilie Vestrheim Thomsen3,4,5, Line Bjørge4,5
1Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Objective:
Patients with ovarian cancer (OC) may develop anti-Yo-associated paraneoplastic cerebellar degeneration (PCD)-a cerebellar ataxia associated with tumor-induced autoimmunity against CDR2 and CDR2L proteins. Dysregulation of circulating exosomal microRNAs (miRNAs) occur in OC. Here, we investigated whether PCD is associated with changes in the exosomal miRNA profiles of OC patients.
Methods:
Serum exosomes were isolated from patients with OC (n = 15), patients with OC and anti-Yo-associated PCD (n = 14) and healthy controls (HC, n = 15). Small RNA sequencing was used to identify differentially expressed miRNAs. Receiver operating characteristic curves were used to evaluate biomarker sensitivity and specificity, and miRNA target prediction analysis was employed to elucidate gene targets.
Results:
OC patients with PCD exhibited a distinct exosomal miRNA expression profile. We detected 103 differentially expressed exosomal miRNAs in PCD patients compared to OC patients without PCD and 139 differentially expressed exosomal miRNAs compared to controls. Particularly miR-486-5p, miR-4732-5p, miR-98-5p and miR-21-5p exhibited notable sensitivity and specificity for discriminating PCD patients from both OC patients without PCD and healthy controls. miRNA target prediction showed that several of the differentially expressed miRNAs in PCD patients targeted the CDR2 and CDR2L genes.
Interpretation:
Our results demonstrate that OC patients with anti-Yo-associated PCD exhibit a distinct exosomal miRNA profile compared to OC patients without PCD. Several of the differentially expressed exosomal miRNAs in PCD patients showed diagnostic potential and may hold relevance for understanding the pathogenesis of PCD.
Insights
Ovarian cancer patients with paraneoplastic cerebellar degeneration (PCD) show distinct exosomal microRNA profiles. Specific microRNAs may serve as biomarkers for diagnosing PCD in ovarian cancer patients.
Area of Science:
- Neuro-oncology
- Molecular diagnostics
- Autoimmune disorders
Background:
- Ovarian cancer (OC) can lead to anti-Yo-associated paraneoplastic cerebellar degeneration (PCD), an autoimmune condition.
- Circulating exosomal microRNAs (miRNAs) are dysregulated in OC, suggesting a potential role in PCD pathogenesis.
Purpose of the Study:
- To investigate if PCD in OC patients is associated with altered exosomal miRNA profiles.
- To identify potential exosomal miRNA biomarkers for PCD in OC.
Main Methods:
- Serum exosomes were isolated from OC patients with and without PCD, and healthy controls.
- Small RNA sequencing identified differentially expressed miRNAs.
- Target prediction analysis explored relationships between miRNAs and relevant genes (CDR2, CDR2L).
Main Results:
- OC patients with PCD displayed distinct exosomal miRNA profiles compared to OC patients without PCD and healthy controls.
- 103 differentially expressed miRNAs were found in PCD patients versus OC patients, and 139 versus controls.
- Specific miRNAs (e.g., miR-486-5p, miR-21-5p) showed high diagnostic potential for PCD.
Conclusions:
- Distinct exosomal miRNA profiles characterize OC patients with anti-Yo-associated PCD.
- Several differentially expressed exosomal miRNAs hold diagnostic potential for PCD in OC.
- These findings contribute to understanding PCD pathogenesis.
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