Circulating microRNA biomarker studies: pitfalls and potential solutions

Area of Science:

• Biomarkers
• Molecular Diagnostics
• Cancer Research

Background:

• Circulating microRNAs (miRNAs) are investigated as biomarkers for disease risk, diagnosis, prognosis, and treatment monitoring.
• Neoplastic diseases show potential for miRNA biomarkers due to cancer cell alterations reflected in extracellular space.
• Current evaluation of miRNA biomarkers reveals challenges in diagnostic specificity and reproducibility.

Purpose of the Study:

• To review issues affecting the diagnostic specificity and reproducibility of circulating miRNA studies.
• To examine the breast cancer literature as a case study for miRNA biomarker consistency.
• To propose improvements for enhancing the diagnostic specificity and reliability of miRNA biomarkers.

Main Methods:

• Literature review focusing on circulating miRNA studies, particularly in breast cancer.
• Analysis of reported miRNA consistency and underlying assumptions in biofluid miRNA profiling.
• Identification of challenges and suggestions for improving miRNA biomarker reliability.

Main Results:

• Few circulating miRNAs are consistently reported across studies, indicating a lack of reproducibility.
• Assumptions about direct contributions of diseased tissue to biofluid miRNA profiles may be flawed.
• Significant challenges exist in achieving reliable and specific circulating miRNA biomarkers.

Conclusions:

• Focusing on miRNAs within specific carriers, such as extracellular vesicles, is crucial for reliable biomarker development.
• Development of alternative sampling techniques and consideration of non-blood biofluids are recommended.
• Standardization of preanalytical and analytical methods is essential for ensuring the reliability of future miRNA biomarker findings.