Peripheral Biofluids Research Articles

MicroRNA Profiles in Parkinson's Disease Prefrontal Cortex.

Objective: The goal of this study was to compare the microRNA (miRNA) profile of Parkinson's disease (PD) frontal cortex with normal control brain, allowing for the identification of PD specific signatures as well as study the disease-related phenotypes of onset age and dementia.Methods: Small RNA sequence analysis was performed from prefrontal cortex for 29 PD samples and 33 control samples. After sample QC, normalization and batch correction, linear regression was employed to identify miRNAs altered in PD, and a PD classifier was developed using weighted voting class prediction. The relationship of miRNA levels to onset age and PD with dementia (PDD) was also characterized in case-only analyses.Results: One twenty five miRNAs were differentially expressed in PD at a genome-wide level of significance (FDR q < 0.05). A set of 29 miRNAs classified PD from non-diseased brain (93.9% specificity, 96.6% sensitivity). The majority of differentially expressed miRNAs (105/125) showed an ordinal relationship from control, to PD without dementia (PDN), to PDD. Among PD brains, 36 miRNAs classified PDD from PDN (sensitivity = 81.2%, specificity = 88.9%). Among differentially expressed miRNAs, miR-10b-5p had a positive association with onset age (q = 4.7e-2).Conclusions: Based on cortical miRNA levels, PD brains were accurately classified from non-diseased brains. Additionally, the PDD miRNA profile exhibited a more severe pattern of alteration among those differentially expressed in PD. To evaluate the clinical utility of miRNAs as potential clinical biomarkers, further characterization and testing of brain-related miRNA alterations in peripheral biofluids is warranted.

Lung cancer screening beyond low-dose computed tomography: the role of novel biomarkers.

Lung cancer is the most common and lethal malignancy in the world. The landmark National lung screening trial (NLST) showed a 20% relative reduction in mortality in high-risk individuals with screening low-dose computed tomography. However, the poor specificity and low prevalence of lung cancer in the NLST provide major limitations to its widespread use. Furthermore, a lung nodule on CT scan requires a nuanced and individualized approach towards management. In this regard, advances in high through-put technology (molecular diagnostics, multi-gene chips, proteomics, and bronchoscopic techniques) have led to discovery of lung cancer biomarkers that have shown potential to complement the current screening standards. Early detection of lung cancer can be achieved by analysis of biomarkers from tissue samples within the respiratory tract such as sputum, saliva, nasal/bronchial airway epithelial cells and exhaled breath condensate or through peripheral biofluids such as blood, serum and urine. Autofluorescence bronchoscopy has been employed in research setting to identify pre-invasive lesions not identified on CT scan. Although these modalities are not yet commercially available in clinic setting, they will be available in the near future and clinicians who care for patients with lung cancer should be aware. In this review, we present up-to-date state of biomarker development, discuss their clinical relevance and predict their future role in lung cancer management.

IDENTIFYING MARKERS OF MICROGLIA ACTIVATION IN CSF FROM PATIENTS WITH ALZHEIMER'S DISEASE USING A NOVEL MASS SPECTROMETRY APPROACH

The aim of the study was to apply the TMTcalibrator+ MS approach to explore the possibility of detecting markers of microglial activation in the CSF, and comparing the levels of such proteins in the CSF of AD patients compared to non-AD controls. We hypothesise that an early event in neurodegenerative pathology involves activation of microglial cells that will secrete distinct proteins into the brain and subsequently into CSF and ultimately plasma. The challenge is how to find these molecules in a readily available biofluid. Traditional unbiased proteomic approaches have struggled to detect low abundance markers due to the high dynamic range of plasma and CSF proteins, and the predominance of plasma albumin and other hyper-abundant proteins. To improve biomarker discovery in peripheral fluids, we developed TMTcalibrator+; a novel MS workflow. Here the use of isobaric Tandem Mass Tags (TMT) allows reference tissue or cell line samples to be labelled and mixed into equivalently labelled samples of peripheral biofluids at a concentration sufficient to ensure the vast majority of MS/MS acquisitions are made on reference-derived peptides. In this study, we analysed the peptides present in the CSF from AD and non-AD patients that are common to activated microglia cells to determine which activated microglial proteins are also found in CSF and which, if any, are differentially expressed in AD compared to individuals with normal cognitive function.