Universal Plasma
microRNAs as Biomarkers in Plasma
MicroRNAs (miRNAs) are small non-coding RNAs found in eukaryotic organisms that regulate gene expression. Dismissed as "junk" until about a decade ago, it is now widely accepted that they play an important functional role in a wide array of cellular processes.
MiRNAs regulate gene expression by targeting individual or multiple messenger RNAs (mRNAs). Perfect or partial base pairing with the target mRNA promotes cleavage of the RNA in plants and inhibition of protein translation in animals. Many studies have demonstrated that dysregulation of these miRNAs is associated with various diseases suggesting there is potential for use of miRNAs in diagnosis and treatment.
Much of the study of miRNA and disease has focused on cancer and neurological disorders. Not surprising since cancer is the leading cause of death worldwide in 2010 and it is estimated that neurological disorders may affect as many as a billion people. There are urgent needs for early diagnosis and treatment in both areas.
Several miRNAs have been linked with various types of cancer due to their regulatory role in cellular development, including: differentiation, proliferation, and apoptosis. Neural miRNAs are known to be involved at various stages of synaptic development, including: dendritogenesis, synapse formation and synapse maturation. Since miRNAs exhibit specific expression profiles in tissues and tumor cells it makes sense that they could serve as biomarkers for these and other diseases.
The study of miRNA function to date has been performed mainly through collection of these tissues by invasive methods. In a clinical setting, more convenient and non-invasive methods are required, such as collection of peripheral blood or other bodily fluids. Recently, it has been demonstrated that miRNAs are present in circulating blood plasma, protected from degradation by inclusion in lipid or lipoprotein complexes. This represents a potential new approach for diagnostic screening in blood. Indeed, characteristic changes in the serum or plasma miRNA profiles of several cancers or other conditions have identified unique signatures that could be exploited as novel biomarkers in the clinic.
Pancreatic cancer (PC) has the poorest overall survival rate among all human cancers because of late diagnosis and absence of screening tools. Researchers at the Karmanos Cancer Institute, Wayne State University set out to develop novel, sensitive, and non-invasive biomarkers of PC using plasma samples1. Utilizing microarray analysis, they found many dysregulated miRNAs in the plasma of patients diagnosed with PC compared to healthy patients and that the expression of some miRNAs correlated well with survival. These results suggest that identifying and validating the expression of miRNAs in newly diagnosed patients could serve as potential biomarker for tumor aggressiveness. Such miRNAs could be useful for the screening of high-risk patients, and may also serve as targets for future drug development.
Traumatic brain injury (TBI) is a major cause of death and disability among young adults in the United States. While altered sensory, motor, cognitive function, and head computed tomography (CT) scans are routinely used to diagnose TBI and to assess injury severity, the availability of a blood-based diagnostic test would supplement clinical assessment and management of TBI patients. Researchers at the Smith Center for Neurologic Research, The University of Texas Health Science Center examined if plasma miRNA levels are altered in patients with TBI relative to matched healthy volunteers, and their potential for use as diagnostic TBI biomarkers2. The plasma miRNA profiles from severe traumatic brain injury (TBI) patients and age-, gender-, and race-matched healthy volunteers were compared by microarray analysis. Of the 108 miRNAs identified in healthy volunteer plasma, about half were altered after severe TBI. Further analysis indicated that several miRNAs were good markers of severe TBI and that combining these miRNAs markedly increased diagnostic accuracy. These results demonstrate that circulating miRNA levels are altered after TBI, providing a rich new source of potential molecular biomarkers. Plasma-derived miRNA biomarkers, used in combination with established clinical practices such as imaging, neurocognitive, and motor examinations, have the potential to improve TBI patient classification and possibly management.
- Ali S, Almhanna K, Chen W, Philip PA, Sarkar FH. (2010) Differentially expressed miRNAs in the plasma may provide a molecular signature for aggressive pancreatic cancer. Am J Transl Res [Epub ahead of print]. [article]
- Redell JB, Moore AN, Ward Iii NH, Hergenroeder GW, Dash PK. (2010) Human traumatic brain injury alters plasma microRNA levels. J Neurotrauma [Epub ahead of print]. [abstract]
About the Author
More than 20 years experience at early stage Biotechnology companies encompassing both product/process development work and entrepreneurial business development work. Mr. Hebel now acts as a consultant to early stage companies developing and commercializing various biotechnology products based on cutting edge technologies.
Kubrick's Damned Spot (3/3).mov
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