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Challenges in using circulating miRNAs as cancer biomarkers.

Tiberio P, Callari M, Angeloni V, Daidone MG, Appierto V - Biomed Res Int (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Biomarker Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy.

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.

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Related in: MedlinePlus

Proposed workflow for circulating miRNA studies.
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fig2: Proposed workflow for circulating miRNA studies.

Mentions: Once hemolyzed samples are identified (independently of the approach used), the choice of removing them from miRNA analysis could be questionable. In fact, in our opinion, circulating miRNA studies should be performed following the workflow proposed in Figure 2. Briefly, after hemolysis evaluation, all samples have to be subjected to miRNA detection, but only nonhemolyzed samples have to be initially used for marker discovery. Then, when interesting miRNAs have been identified, researchers should determine whether (and in what extent) the identified miRNAs are hemolysis affected. If identified miRNAs are not influenced by hemolysis, hemolyzed samples could be recovered and included in the analysis.


Challenges in using circulating miRNAs as cancer biomarkers.

Tiberio P, Callari M, Angeloni V, Daidone MG, Appierto V - Biomed Res Int (2015)

Proposed workflow for circulating miRNA studies.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385632&req=5

fig2: Proposed workflow for circulating miRNA studies.
Mentions: Once hemolyzed samples are identified (independently of the approach used), the choice of removing them from miRNA analysis could be questionable. In fact, in our opinion, circulating miRNA studies should be performed following the workflow proposed in Figure 2. Briefly, after hemolysis evaluation, all samples have to be subjected to miRNA detection, but only nonhemolyzed samples have to be initially used for marker discovery. Then, when interesting miRNAs have been identified, researchers should determine whether (and in what extent) the identified miRNAs are hemolysis affected. If identified miRNAs are not influenced by hemolysis, hemolyzed samples could be recovered and included in the analysis.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Biomarker Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy.

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.

Show MeSH
Related in: MedlinePlus