Challenges in using circulating miRNAs as cancer biomarkers

Area of Science:

• Biomarkers
• Molecular Oncology
• Cancer Diagnostics

Background:

• Circulating microRNAs (miRNAs) are emerging as promising biomarkers for cancer diagnosis, prognosis, and treatment monitoring.
• Despite initial enthusiasm, inconsistencies across studies limit the clinical application of miRNA-based tools.
• Preanalytical and analytical variables, along with donor-related factors, contribute to unreliable circulating miRNA quantification.

Purpose of the Study:

• To review potential technical biases and individual-related parameters affecting circulating miRNA studies.
• To highlight critical issues in sample handling, processing, and data normalization.
• To emphasize the need for standardized protocols for accurate circulating miRNA detection.

Main Methods:

• Literature review of studies on circulating miRNAs as cancer biomarkers.
• Analysis of preanalytical and analytical variables impacting miRNA quantification.
• Discussion of donor-related factors and sample processing inconsistencies.

Main Results:

• Widespread inconsistencies observed in circulating miRNA studies due to technical and individual-related factors.
• Nonuniform sample handling, blood cell contamination, and lack of normalization consensus are key issues.
• Artefacts generated by these variables impair accurate circulating miRNA quantification.

Conclusions:

• Circulating miRNAs hold significant potential for advancing cancer management.
• Clinical validation requires addressing inconsistencies through standardized procedures and global consensus.
• Standardized protocols are essential to prove the clinical significance of circulating miRNAs in oncology.