Biomarker Failure

(May 15th, 2015) miRNAs are considered important molecules for the prediction of cancer. However, a new study suggests that, at the moment, miRNAs do not provide data reliable enough for the identification of early stage melanoma.

Diagnosing cancer early to start treatment as soon as possible is one of medicine’s holy grails. Therefore, researchers and physicians look for telltale signs or biomarkers in tumour tissue or serum/plasma samples. For some time, miRNAs were thought to be suitable but Christiane Margue and colleagues from the University of Luxembourg in collaboration with Klinikum Dortmund in Germany collected data speaking against the use of miRNAs for the detection of early stage melanoma. Originally, the team’s goal was to define a healthy human miRNome and to understand whether it can be used to predict cancer development.

A miRNome is defined as all miRNAs found in an organism. “In humans, there are currently around 2,500 mature miRNAs and the number is still rising,” says Stefanie Kreis, corresponding author of the recent study. miRNAs are small, non-coding RNA molecules involved, for instance, in RNA silencing and post-transcriptional regulation of gene expression. Importantly, they can enter the bloodstream and be easily detected by laboratory tests. Some believe types and amounts of miRNAs are indicative of cancer development due to the changes in miRNA expression pattern found in affected tissue way before the patient can feel any symptoms.

The Luxembourg researchers analysed 126 blood samples by whole miRNome and custom qPCR arrays, hoping that miRNAs can be used as biomarkers. However, the team was very surprised to find that, at least in melanoma, miRNA levels and types do not correlate with early stage development of the disease.

“In our study, we show that blood-based miRNAs are not suitable to predict early stage melanoma cancers when a biomarker would be most useful. Applying rigid quality controls, miRNAs only turned out to be useful in confirming late stage diseases when biomarkers are generally not required any more. With the current state of sensitivity and specificity, blood based miRNAs might not be the sought-after biomarkers for early detection of cancers. We need to improve the quality of miRNA detection and quantification, before they can be routinely used in clinically useful tests. A first step towards this was done here by putting together a ‘healthy miRNome’, which is an important reference for any kind of study on cancers or other diseases,” says Stephanie Kreis. She also adds that “we were surprised to see that the healthy miRNome in the blood is very stable.”

The Margue team also speculates that miRNAs would not be useful biomarkers in the detection of other types of cancers. Still, the researchers are hopeful that they “can achieve the goal of using miRNAs as biomarkers” once “the scientific community agrees on general quality standards for sample processing, detection and quantification of miRNAs”.

Nadejda Capatina

Photo: Hodan

Last Changes: 06.30.2015