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Extracellular RNAs: development as biomarkers of human disease.

Quinn JF, Patel T, Wong D, Das S, Freedman JE, Laurent LC, Carter BS, Hochberg F, Van Keuren-Jensen K, Huentelman M, Spetzler R, Kalani MY, Arango J, Adelson PD, Weiner HL, Gandhi R, Goilav B, Putterman C, Saugstad JA - J Extracell Vesicles (2015)

Bottom Line: Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described.These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid.Progress to date and the plans for future studies are outlined.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR, USA; quinnj@ohsu.edu.

ABSTRACT
Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

No MeSH data available.


Related in: MedlinePlus

ERCC biomarker groups.
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Figure 0001: ERCC biomarker groups.

Mentions: Clinical research across the spectrum of human disease is challenged by the immense cost of testing experimental therapeutics in human subjects. In every subspecialty of medicine, there is a need for surrogate markers of disease for the purposes of identifying subjects at risk, documenting “target engagement” and objectifying treatment outcomes in a manner that will permit “proof of concept” trials with feasible numbers of subjects and a reasonable duration of treatment. A targeted approach to identification and validation of such biomarkers has been successful in some arenas, such as the use of glycosylated haemoglobin for monitoring diabetes mellitus or use of quantitative viral load for monitoring HIV therapy. Non-targeted empirical approaches using proteomics and metabolomics have also seen some success, so it follows logically that microRNAs (miRNAs) are now being evaluated as biomarkers in a variety of human diseases. It remains to be seen whether miRNAs will be more informative or more useful than protein biomarkers, particularly as new methodologies make it possible to focus on exosomal proteins rather than total protein, and on exosomes derived from specific organs (1). A discussion of the utility of exosomal protein biomarkers is beyond the scope of this review, but the emphasis here on miRNA should not be interpreted as a conclusion that we have no more to learn from protein biomarkers. The focus on miRNAs is simply a reflection of the nature of the consortium being reviewed here. As described elsewhere in this issue, the NIH Common Fund Extracellular RNA Communication Program has funded 10 UH2/UH3 grants to identify extracellular RNA (exRNA) biomarkers in conditions ranging from gastric cancer to Alzheimer's disease (AD), relying on body fluids ranging from saliva to cerebrospinal fluid (CSF). This funding mechanism is relatively unique within the NIH, funding “high risk,” “discovery” work over the first 2 years in a “UH2” phase, with each project advancing to more traditional NIH-funded hypothesis testing in years 3–5 of “UH3” funding, dependent on the attainment of predefined milestones. Each of these projects is currently in a “discovery” phase after about 1 year of activity. We review here the rationale, methods and progress of the UH2 projects, summarized in Table I. Both the table and the following text are listed according to organ system studied and the relevant body fluid analyzed, as depicted in Fig. 1. Since clinical phenotyping of the samples is so critical to the success of the projects, the clinical cohort for each is also indicated.


Extracellular RNAs: development as biomarkers of human disease.

Quinn JF, Patel T, Wong D, Das S, Freedman JE, Laurent LC, Carter BS, Hochberg F, Van Keuren-Jensen K, Huentelman M, Spetzler R, Kalani MY, Arango J, Adelson PD, Weiner HL, Gandhi R, Goilav B, Putterman C, Saugstad JA - J Extracell Vesicles (2015)

ERCC biomarker groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553262&req=5

Figure 0001: ERCC biomarker groups.
Mentions: Clinical research across the spectrum of human disease is challenged by the immense cost of testing experimental therapeutics in human subjects. In every subspecialty of medicine, there is a need for surrogate markers of disease for the purposes of identifying subjects at risk, documenting “target engagement” and objectifying treatment outcomes in a manner that will permit “proof of concept” trials with feasible numbers of subjects and a reasonable duration of treatment. A targeted approach to identification and validation of such biomarkers has been successful in some arenas, such as the use of glycosylated haemoglobin for monitoring diabetes mellitus or use of quantitative viral load for monitoring HIV therapy. Non-targeted empirical approaches using proteomics and metabolomics have also seen some success, so it follows logically that microRNAs (miRNAs) are now being evaluated as biomarkers in a variety of human diseases. It remains to be seen whether miRNAs will be more informative or more useful than protein biomarkers, particularly as new methodologies make it possible to focus on exosomal proteins rather than total protein, and on exosomes derived from specific organs (1). A discussion of the utility of exosomal protein biomarkers is beyond the scope of this review, but the emphasis here on miRNA should not be interpreted as a conclusion that we have no more to learn from protein biomarkers. The focus on miRNAs is simply a reflection of the nature of the consortium being reviewed here. As described elsewhere in this issue, the NIH Common Fund Extracellular RNA Communication Program has funded 10 UH2/UH3 grants to identify extracellular RNA (exRNA) biomarkers in conditions ranging from gastric cancer to Alzheimer's disease (AD), relying on body fluids ranging from saliva to cerebrospinal fluid (CSF). This funding mechanism is relatively unique within the NIH, funding “high risk,” “discovery” work over the first 2 years in a “UH2” phase, with each project advancing to more traditional NIH-funded hypothesis testing in years 3–5 of “UH3” funding, dependent on the attainment of predefined milestones. Each of these projects is currently in a “discovery” phase after about 1 year of activity. We review here the rationale, methods and progress of the UH2 projects, summarized in Table I. Both the table and the following text are listed according to organ system studied and the relevant body fluid analyzed, as depicted in Fig. 1. Since clinical phenotyping of the samples is so critical to the success of the projects, the clinical cohort for each is also indicated.

Bottom Line: Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described.These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid.Progress to date and the plans for future studies are outlined.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR, USA; quinnj@ohsu.edu.

ABSTRACT
Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

No MeSH data available.


Related in: MedlinePlus