Challenges in Using Circulating miRNAs as Cancer Biomarkers

Abstract

In the last years, circulating miRNAs have emerged as a new class of promising cancer biomarkers. Independent studies have shown the feasibility of using these small RNAs as tools for the diagnosis and prognosis of different types of malignancies as well as for predicting and possibly monitoring treatment response. However, despite an initial enthusiasm for their possible clinical application, widespread inconsistencies have been observed among the studies, and miRNA-based tools still represent the object of research within clinical diagnostic or treatment protocols. The poor overlap of results could be explained, at least in part, by preanalytical and analytical variables and donor-related factors that could generate artefacts, impairing an accurate quantification of circulating miRNAs. In fact, critical issues are represented by nonuniform sample choice, handling, and processing, as well as by blood cell contamination in sample preparation and lack of consensus for data normalization. In this review, we address the potential technical biases and individual-related parameters that can influence circulating miRNA studies' outcome. The exciting potential of circulating miRNAs as cancer biomarkers could confer an important advance in the disease management, but their clinical significance might not be proven without a global consensus of procedures and standardized protocols for their accurate detection.

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…incorrect selection or poor representativeness of the patient groups, incorrect processing and storage of the specimens and insufficient statistical power of the study). There is also no consensus on the normalisation method used for the resulting data, which is why all steps of an analytical procedure must be validated and standardised before any miRNA-based diagnostic method can be implemented into clinical practice [76].…”

Epigenetic regulation by DNA methylation and miRNA molecules in cancer

“…Overall, circulating miRNA findings require further steps of validation and a standardization of all procedures, in order to control for all potential technical biases. In addition, other external factors and lifestyle that could contribute to affect miRNA levels in the circulation should also be considered in the evaluation of circulating miRNA profiles [27].…”

Problems, challenges and promises: perspectives on precision medicine

“…Metabolomics and the sequencing of circulating microRNAs and cell-free DNA will likely prove key to the ongoing assessment of health and disease by providing a non-invasive means of charting changes in disease states, using bodily fluids [27][28][29][30].…”