miRNAs: potent biomarkers in cancer research?

journal.pone.0118220.g002

Expression signals of validated miRNAs that differentiated pancreato-biliary cancer from non-malignant abnormalities (A), or from cancers of other types (B).

A recent paper by Kojima, M. et al. has found a signature of miRNAs to identify patients with pancreato-biliary cancers who could benefit from surgical intervention.

Namely, a combination of eight miRNAs (miR-6075, miR-4294, miR-6880-5p, miR-6799-5p, miR-125a-3p, miR-4530, miR-6836-3p, and miR-4476) achieved a sensitivity, specificity, accuracy and AUC of 80.3%, 97.6%, 91.6% and 0.953, respectively.

In contrast, CA19-9 and CEA gave sensitivities of 65.6% and 40.0%, specificities of 92.9% and 88.6%, and accuracies of 82.1% and 71.8%, respectively, in the same test cohort. This diagnostic index identified 18/21 operable pancreatic cancers and 38/48 operable biliary-tract cancers in the entire cohort.

Finding of this eight miRNAs was possible by using Toray’s 3D profiling technology. This finding is especially important, as it is difficult to detect pancreatic cancer or biliary-tract cancer at an early stage using current diagnostic technology.

microRNAs are stably present in peripheral blood, and are therefore a good candidate for finding prognostic or diagnostic biomarkers.

Studying only the miRNAs available in the literature may limit the novelty of the biomarkers found, so for a wide variety of diseases, a profiling is mandatory in order to find really specific circulating biomarkers.

Toray’s technology is available in Europe as fee-for-services via tebu-bio Laboratories (see Press Release). By exploring the full miRnome (composed by 2,000 miRNAs) with Toray’s 3D-Gene® technology, one might identify slight miRNA expression level changes (including low abundance miRNAs) in blood samples, biopsies FFPE specimens…

Interested in miRNA profiling in cancer research? Leave a message below or browse tebu-bio’s 3D-Gene® miRNA profiling platform web page!

Cytokine signature in airway inflammation with arrays

Chronic Mucosal Inflammation is the hallmark of common airway diseases (ex.  Allergic Rhinitis and asthma). Lipoxin B4(LXB4) is an endogenous mucosal protective mediator decreasing such diseases. LXB4 mechanisms of action remain poorly understood.

Cytokine Quantibody Arrays from Raybiotech and tebu-bio laboratories

Cytokine Quantibody Arrays from Raybiotech and tebu-bio laboratories.

In a recent paper in Mucosal Immunology (Karra, L. et al. (2015) 8; DOI:10.1038/mi.2014.116), Allergic Rhinitis  and asthma murine models have been described to better investigate the role of LXB4 in Mucosal Inflammation. The authors conclude that, in the upper airway, LXB4 significantly decreases nasal mucosal leukocytes and degranulation of Mast Cells (MCs) and Eosinophils. They also show that, in the lower airway, LXB4 significantly decreased airway inflammation, mucus metaplasia, and hyper-responsiveness.

Inhibition of MC degranulation in vivo by LXB4 is more potent than Dexamethasone (a well-known apoptosis inducing glucocorticoid) with unique profiles for cytokine regulation. This latter  is proved by  quantitative analysis of 20 murine cytokines in a single array (Quantibody Cytokine Array).

These findings indicate that LXB4 carries cell type selective and mucosal protective actions and need to be translated to human models. This publication opens the way to consider lipoxins as new therapeutical candidates.

tebu-bio: European RaybioTech's Certified Laboratory service provider

tebu-bio laboratories are the European RaybioTech’s Certified Laboratory service provider.

The Cytokine Arrays are available as ready-to-use assays. They can also be outsourced to Certified Service Laboratory Providers as fee-for-services. In that case, researchers just send their samples and in return receive the experimental data set. To ensure top quality in the data obtained, Raybiotech’s service providers successfully complete training and certification programs to receive the “RayBiotech Certified Array Service Providers” yellow award.

In Europe, tebu-bio laboratories (France) were among the first laboratories in the world to be certified by Raybiotech in 2012. tebu-bio’s services also cover Quansys BioSciences and FullMoon BioSystems technologies for outsourcing protein profiling and quantification.

More data with chemiluminescence imaging platform

Quansys Q-View Imager Pro. Source: tebu-bio.

Quansys Q-View Imager Pro. Source: tebu-bio.

Depending on the phase where your biomarker-related research program is, imaging of protein or antibody arrays has different requirements. For R&D purposes (incl. translational and preclinical ones), a standard imager is more than enough. However, for clinical assays at the late stages, a higher resolution may be needed, especially in view of a future file submission.

Known for the development of the Q-plex platform, which is being used by translational and clinical laboratories worldwide (e.g. to detect Pneumococcus), Quansys has released a new imager, designed for higher throughput (96- and 384-well plates) and clinical-grade research. [Read more…]

Identification of a MicroRNA signature for Fibromyalgia diagnosis

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Heatmap of PBMCs miRNome from FM patients and controls. The microarray analysis was performed with Toray’s 3D-Gene Human miRNA Oligo chips (v.16.0; current version is v21.0). Patient samples are labeled (FM 1–11) and controls (C 1–10). Color palette is included to indicate signal intensity.

A recent paper by Cerdá-Olmedo, G. et al. unravels the miRNA signature in fibromyalgia (FM). Diagnosis of FM, a chronic musculoskeletal pain syndrome characterised by generalized body pain, hyperalgesia and other functional and emotional comorbidities, is a challenging process hindered by symptom heterogeneity and clinical overlap with other disorders. No objective diagnostic method exists at present.

This study aimed at identifying changes in miRNA expression profiles (miRNome) of FM patients for the development of a quantitative diagnostic method of FM. In addition, knowledge of FM patient miRNomes would lead to a deeper understanding of the etiology and/or symptom severity of this complex disease.

A broad profiling was first performed using Toray’s technology. miRNAs found were validated by qPCR in a later step. The profiling of FM patients PBMCs showed a marked downregulation of hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p, hsa-miR145-5p and hsa-miR-21-5p (4-fold or more).

Globally, 20% of the miRNAs analyzed (233/1212) showed downregulation of at least 2-fold in patients. This might indicate a general de-regulation of the miRNA synthetic pathway in FM. No significant correlations between miRNA inhibition and FM cardinal symptoms could be identified. However, the patient with the lowest score for mental fatigue coincided with the mildest inhibition in four of the five miRNAs associated with the FM-group.

Therefore, the authors propose a signature of five strikingly downregulated miRNAs (hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p and hsa-miR145-5p) to be used as biomarkers of FM. Validation in larger study groups would be required before the results can be transferred to the clinic, as the authors indicate.

Looking for miRNA signatures? Don’t hesitate to leave your comments below!

miRNAs and Autoimmune Glomerulonephritis

Correlation of findings in animal models (e.g. mouse) and its validation in human samples lies at the basis of Translational medicine. Nowadays, hypothesis established in mouse models must, at some stage, be validated in a cohort of patients. [Read more…]

Which approach for measuring circulating cell-free miRNAs?

More than 2,500 human miRNAs are potentially significant biomarkers. Moreover, the use of blood circulating miRNAs as disease-specific biomarkers is one of the most valuable outputs for translational and clinical research. Nevertheless, such an analysis still requires the selection of robust technologies, huge R&D work and reproducibility studies.

During the latest AACR Meeting (April 2015, Philadelphia – USA), Nadia Normand, R&D manager at tebu-bio’s laboratories (Le Perray en Yvelines, France), presented a poster comparing various platforms for measuring circulating miRNAs. It was the opportunity to further demonstrate the robustness of  the miRNA 3D-Gene® microarray-based platform (Toray Industries).

To know more about the comparison, follow this link to access to the poster:

Mennesson E. et al. “Comparison of different highly sensitive miRNA array platforms for the investigation of circulating cell-free microRNAs in blood” (2015) – Poster AACR.

 

Tumour microenvironment – glycosylation

Cancer research is increasingly focusing on the tumour microenvironment (TME). Several studies have shown that tumours depend on external signals for maintenance and expansion. It is therefore needed to have a deeper knowledge of the cross-talk between tumour cells in the stroma (fibroblasts, adipocytes, endothelial cells and macrophages) and their microenvironment which also includes the study of interactions between cancer cells and cancer stem cells. TME studies also involve soluble factors, signaling molecules, extracellular matrix proteins (ECM) and other factors that help the tumour grow and invade other tissues, protect it from the host immune system, and contributes to therapeutic resistance in some cases (1). In a previous post, we discussed the role of Cox-2 signaling and PGE2 in TME. Also, we have already discussed the role of inflammation and the modification of the host’s immune response by cancer cells.

Today, we would like to focus on how TME affects the glycosylation of proteins involved in tumour progression.

[Read more…]

Interactions between cancer and immune cells via cytokine networks

Pr. Ruo-Pan Huang’s team has just published a review detailing the interactions between cancer and immune cells.

This overview describes the key cytokine signals, cell–cell signal networks in the tumor microenvironment during cancer diseases. It also demonstrates the power of antibody arrays and multiplex immunoassays as unique research tools to decipher cytokine networks during cancer and inflammation processes.

Source:

Brett Burkholder et al. “Tumor-induced perturbations of cytokines and immune cell networks” (2014) BBA – Reviews on Cancer, Vol. 1845 no. 2, 182–201. DOI http://dx.doi.org/10.1016/j.bbcan.2014.01.004

Histone Peptide Arrays’ contribution in Epigenetic studies

EpiGold™ Histone Peptide Array Data-FluorescenceDNA methylation and histone post-translational modifications are key epigenetic factors.

They regulate gene expression by interfering with the chromatin structure and the binding of effector proteins to post-translational modified histones (1).

Several experimental strategies to analyze such binding have recently been designed; histone modified peptide arrays being one of them. [Read more…]