Circulating exosomal miRNAs: clinical significance in human cancers

ABSTRACT

Introduction: The identification of novel noninvasive biomarkers to ameliorate early-diagnosis, and disease prognosis, as well as to support personalized treatment and monitoring decisions is of first clinical priority for cancer patients’ care. Exosomes are natural endosome-derived extracellular vesicles that have emerged as crucial mediators of intercellular communication and tumor progression. Considering that deregulated miRNA levels have been described in numerous human malignancies and that tumor-derived exosomes reflect miRNA expression of donor tumor cells, the evaluation of exosome-derived circulating miRNAs (exomiRs) may offer a new promising class of noninvasive molecular markers to improve patients’ management and quality-of-life.

Areas covered: In the current review we have summarized the existing knowledge on the clinical relevance of circulating exosomal miRNAs in improving cancer diagnosis and prognosis, and thus supporting personalized patients’ management

Expert commentary: Cancer research has highlighted the abundance of exomiRs in patients’ plasma and serum samples, as well as their biomarker capabilities in the vast majority of human malignancies studied so far. Their analytical stability constitutes exomiRs ideal molecular markers to overcome numerous limitations of cancer clinical management, while future large-scale studies should unveil exomiRs translational utility in modern cancer molecular diagnostics.

KEYWORDS:

• Circulating miRNA
• exomiR
• exosomes
• non coding RNA
• noninvasive biomarkers

Article highlights

• Tumor-derived exosomes reflect the gene expression profile of tumor cells and could be utilized in modern molecular diagnostics.

• Tumor-derived exosomes constitute bioactive vesicles that mediate intercellular interactions and modulate intracellular processes of the recipient cells, facilitating disease progression

• Exosomal circulating miRNAs are noninvasively accessible, highly stable and easily quantified in plasma/serum samples to support cancer molecular diagnostics.

• Following a decade from the description of circulating miRNAs, numerous exomiRs have been validated so far to benefit cancer patients’ diagnosis and/or prognosis, and thus to support personalized disease management.

• Based on the pre-clinical data so far, selected exosomal miRNAs have to be validated in large-scale clinical studies in order to be selected to enter clinical trials, and finally to be validated for routine clinical use.

• The thorough evaluation of exomiRs’ clinical and biological significance in human malignancies will amplify their translational impact on disease understanding and clinical management.

• The specific isolation and study of tumor-derived exosomes and exomiRs will provide specific knowledge on the cellular physiology and behavior of tumor cells, and, thus, on disease clinical outcome and monitoring.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The research presented was carried out within the framework of a Stavros Niarchos Foundation grant to the National and Kapodistrian University of Athens [GRANT ID 16785].