June 12, 2017

Circulating MicroRNAs Show Biomarker Potential for Canine Cancer

Two circulating microRNAs have shown potential as diagnostic and prognostic biomarkers for an array of canine cancers.
By JoAnna Pendergrass, DVM
Two circulating microRNAs (miRNAs) have demonstrated promising prognostic and diagnostic biomarker potential for a broad spectrum of canine cancers, according to a study published in Scientific Reports. Study results, the authors wrote, “provide foundational information for developing novel miRNA biomarkers for both human and canine tumors.”
 
Human and canine tumors share several similarities, including tumor microenvironment and histopathology; such similarities support the use of canine tumors as ideal models for human tumors. Cancer biomarker identification, however, remains unequal between human and veterinary oncology; clinically useful cancer biomarkers, while identified in human oncology, remain elusive in veterinary oncology.
 
miRNAs, particularly miR-214 and miR-126, influence several aspects of tumorigenesis, including cell proliferation and apoptosis. Circulating miRNA levels are useful for determining treatment response and tumor grade. Interestingly, miRNA sequences are broadly conserved across species.
 
Human studies have reported increased miR-214 or miR-126 levels in several cancer types, including osteosarcoma and breast cancer. To date, veterinary studies have measured circulating levels of these miRNAs only in hemangiosarcomas.
 
Study Design
The authors extracted RNA from 191 plasma samples of healthy dogs and dogs with tumors. Tumors were categorized as epithelial (eg, adenocarcinoma), non-epithelial (eg, hemangiosarcoma), or miscellaneous (eg, genital tumor); healthy samples were the controls. Following RNA extraction, the authors performed reverse transcription polymerase chain reaction (PCR) to measure circulating miR-214 and miR-126 levels.
 
Information on survival duration, cause of death, and clinical parameters was also collected. Clinical parameters included age, histologic diagnosis, and coagulation factors.
 
To determine sequence homology, the authors compared mature canine and human miRNA sequences already registered within an miRNA database; they also compared the study’s miRNA sequences with the database’s human sequences.
 
Results and Discussion
Sequence Homology
The authors identified a 38% sequence homology between the database’s human and canine miRNAs. Notably, the study’s miR-214, miR-126, and miR-16 sequences exactly matched the database’s human sequences.
 
Circulating miRNA Levels
Overall, circulating miR-214 and miR-126 levels were significantly higher in tumors than in controls. Specifically, miR-214 was significantly higher in epithelial and non-epithelial tumors than in controls, with non-epithelial tumors having the highest miR-214 levels. miR-126 was significantly higher in all tumor categories than in controls.
 
When analyzing miRNA levels in individual cancer subtypes, the authors observed no significant differences in levels between miscellaneous tumors and controls.
 
Diagnostic Potential
miR-214 showed the greatest diagnostic potential for non-epithelial tumors, particularly for sarcomas and aggressive sarcomas (e.g., hemangiosarcomas). In contrast, miR-126 diagnostic potential was greatest with epithelial tumors. Interestingly, when combining the miRNAs, diagnostic accuracy significantly improved for both epithelial and non-epithelial tumors.
 
Prognostic Potential
The authors determined prognostic potential by comparing survival durations for high and low levels of each miRNA. For epithelial tumors, survival duration was significantly shorter with high miR-126 than with low miR-126. For non-epithelial tumors (excluding osteosarcomas), survival duration was significantly shorter with high miR-214 than with low miR-214; osteosarcomas were excluded because their exceptionally high miR-214 levels may have obscured survival differences in other non-epithelial tumors.
 
Correlation with Clinical Parameters
The authors observed a generally weak correlation between the miRNAs and clinical parameters, suggesting that miR-214 and miR-126 can be used to assess tumor state “without noise from concurrent disease.”
 
For future studies, the authors suggested measuring circulating levels of miR-214 and miR-126 in non-neoplastic diseases and determining whether these miRNAs are released directly from tumor cells. Overall, the authors concluded that miR-214 and miR-126 “may be key references for exploring novel biomarkers for human cancers.”
 
 
Dr. JoAnna Pendergrass received her Doctor of Veterinary Medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.

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