During 2012, a number of new methods and techniques were reported in the pages of BioTechniques aimed at quickly moving diagnostic applications or therapeutics toward the clinic.
But when the editors sat down as a group to examine the landscape of translational research methods in 2012, two developments seemed to emerge from the pack – an advance in microRNA (miRNA) quantification that should enable the discovery and use of informative miRNA-based biomarkers in the future and a simplified assay using a currently available fluorescent substrate that could impact the diagnosis of gliomas.
Hanna et al. BioTechniques 52:235-245 (2012).
In recent years, miRNAs have emerged as key biological regulators of pathogenesis in many human diseases, including cancer. While the field of RNA interference has seen its up and downs over the past decade, steady progress in moving gene-silencing approaches using small RNAs towards the clinic continues. In addition to their possible roles as therapeutics, identification of miRNA-based biomarkers of disease is important in diagnostic applications. But while initially identifying a prognostic biomarker is a solid start, being able to quantify changes in marker abundance between the disease and normal states can be even more informative. Enter David Rimm and his colleagues at Yale University who in 2012 described the development of a quantitative fluorescence in situ hybridization assay to examine miRNAs in tissue samples. Previously studies of miRNA abundance required the total extraction of RNA from cells, but the problem is that this isolation approach results in the loss of key spatial information (i.e. was the miRNA overexpressed in a specific location in the cell?). By using a variety of dyes and stains, along with miRNA in situ hybridization, Rimm and his colleagues were able to establish the locations of various subcellular compartments in tumor epithelial samples which could then be correlated with the abundance of specific miRNAs, providing spatial information in addition to quantitative values of miRNA abundance. The Yale team also showed that this approach was amenable to high-throughput tissue microarray-based assessment of miRNAs. Taken together, this work represents an important step in the design of a tool set for the discovery and validation of potential diagnostic miRNA biomarkers.
Kucheryavykh et al. BioTechniques 53:305-309 (2012).
Glioblastoma is an extremely malignant form of cerebral glioma. Even though brain imaging and clinical presentation may indicate a glioblastoma, histopathology is still necessary for a definitive diagnosis. In November, a team of researchers described a new tool for the diagnosis of these tumors – 4-(4-(dimethylamino)-styryl)-N-methylpyridinium iodide (ASP+), a well-known substrate for monoamine transporters, can be used as a marker of gliomas. The authors demonstrate that accumulation of this fluorescent substrate can be used to evaluate glioma tumors in brain slices using fluorescence microscopy, thus better enabling clinicians to confirm diagnoses and providing researchers a simple tool to study glioma formation.
Clearly 2012 provided some interesting new methods and tools that can be used for translational research. Importantly, this trend among methods articles, and the clear interest in developing or even applying current tools to translational studies, is on the rise, an encouraging sign for everyone as we are sure to see more basic discoveries drive clinical applications in the near future.