miRNAs: potent biomarkers in cancer research?

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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!

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…]

Meeting Report: RNA and Cancer – Toulouse, 14 Nov. 2014

“Toulouse may be the mRNA translation capital of France” declared third keynote speaker Jerry Pelletier at the symposium organized by Yvan Martineau, Stéphane Pyronnet et Julie Guillermet-Guibert of the CRCT ( Le Centre de recherche en Cancérologie de Toulouse) within the beautiful and modern Oncopole in Toulouse, France.

[Read more…]

Tumour microenvironment and miRNA biomarkers

In previous posts, we have seen the role of inflammation and glycosylation in the tumour microenvironment (TME). All these are mainly factors at the protein level causing the tumour cells to evade the immune system and metastasise. But what about other factors?

One of the areas that has raised quite some interest recently are microRNAs (miRNAs). If you’d like to brush up your knowledge on miRNAs, you might be interested in this post by my colleague Paola Vecino. miRNAs are becoming trendy, as they seem to be involved in several disease mechanisms (not only in cancer, but also in some other pathologies, including some inflammatory diseases), and they can be used as diagnostic and/or prognostic biomarkers.

[Read more…]

microRNAs: Portraying a cell – miRNA profiling

Well, in the previous posts leading up to this final one in the series, we looked at microRNA detection, overexpression, inhibition, and target detection. I’d like to finish by going over miRNA profiling. [Read more…]

microRNAs: Target detection

Leading on from my previous posts (see below) exploring microRNA detection, overexpression and inhibition, this time, let’s spend a moment on target detection.

miTarget databases

There are many online resources to find the target of a given miRNA, such as: [Read more…]

microRNAs: Inhibiting the inhibitors – Antagomirs

Following on in our series on microRNAs (miRNA – Keys to open cell biology’s secret chamber) , in this post, we’ll be taking a look at Antagomirs (which are also called anti-miRs or blockmirs). These chemically engineered oligonucleotides prevent other molecules from binding to a desired site on an mRNA molecule. They’re used to silence endogenous microRNA.

[Read more…]

microRNAs: Finding the effector – miRNA detection

Following on from my previous post  in which I started to introduce a series of techniques to investigate the impact of miRNA expression on cell fate, let’s take a look at the first one: miRNA detection

[Read more…]

microRNAs: Keys to open cell biology’s secret chamber

As cell biologist, when working in labs I have in the past witnessed several “X-files” in a flask of cells along my way: all cells of an established cell line are supposed to have the same genetic background and to respond similarly to the same stimuli… but sometimes this is simply not what happens!
I would not risk saying that it all comes down to epigenetics, but much of this “unexpected” behaviour is governed at  mRNA level independently of the genetic background. “Cell personality” is then defined at several levels: genetic background, epigenetics, mRNA modulation and protein/lipid content.

It’s a sophisticated web of positive/negative signals that governs cell fate and behavior. But how do cells cope with this complicated issue? [Read more…]